back

 

Judy Bolton
Judy L. Bolton, Ph.D.

Professor and Head, Department of Medicinal Chemistry and Pharmacognosy
Director of the Carcinogenesis and Chemoprevention Program, UIC Cancer Center

University of Illinois at Chicago
College of Pharmacy
833 S. Wood Street (M/C 781)
Chicago, IL 60612-7231

Office: 325 PHARM
Office Phone: 312-996-5280
Fax Number: 312-996-7107
E-mail address: judy.bolton@uic.edu

Education:

University of Toronto Ph.D. 1984-1988
University of Toronto B.Sc. 1980-1984
University of Colorado Post-Doctoral Fellow (s) 1988-1992

Research Interests:

Research is conducted to prove the hypotheses proposed in the following 3 NIH funded projects.

  1. Carcinogenic metabolites formed from antiestrogens. Tamoxifen remains the endocrine therapy of choice in the treatment of all stages of hormone-dependent breast cancer. In addition, large-scale clinical trials are in progress to determine the potential of tamoxifen to act as a chemopreventive agent in women considered at high risk for developing breast cancer. However, several studies have raised concern over the safety of chronic treatment with this drug. Alternate antiestrogens including droloxifene, toremifene, and idoxifene, may not be genotoxic probably because of different routes of metabolism which could lead to a decrease in amount and/or type of ultimate carcinogen(s). The central hypothesis of this project is that the formation of reactive intermediates is an important mechanism of carcinogenesis and/or cytotoxicity for certain antiestrogens.
  2. Bioactivation of estrogens to carcinogenic quinoids. There is a clear association between excessive exposure to estrogens and the development of cancer in several tissues including breast and endometrium. The risk factors for women developing these cancers are all associated with longer estrogen exposure; early menses, late menopause, and long term estrogen replacement therapy. The mechanism(s) of estrogen carcinogenesis is not known. The central hypothesis is that the formation of quinoids is an important mechanism of estrogen carcinogenesis. o-Quinones are known metabolites of estrogens..
  3. Estrogenic agents: In vitro and in vivo evaluation. The major objective of Project 2 is to provide in vitro bioassay support for the discovery of the active components for the major dietary supplements. To achieve this objective several in vitro cell based assays are available in order to investigate the mechanism of action of these dietary supplements. Specifically, we are interested in botanicals with health benefits towards pre- and postmenopausal women such as Vitex agnus-castus (VACS), Cimifuga racemosa (CR, black cohosh) and Trifilium pratense (red clover, RC). The hypothesis to be addressed is these plants contain potent estrogenic compounds useful for the relief of menopausal symptoms as well as other beneficial properties of estrogens.

Professional Organizations:

American Chemical Society
Society of Toxicology
International Society for the Study of Xenobiotics (ISSX)
American Association for the Advancement of Science
American Association of Cancer Research

Edited Journals and Honorarium:

2000 - present Listed in Who's Who in America, 55th Edition
2000 - present Associate Editor for Chemical Research in Toxicology
1999 - present Listed in Who's Who in America - Science and Engineering, 5th Edition
1999 - present Listed in Who's Who of American Women, 22nd Edition
1998 - 2001 University Scholar, University of Illinois
1992 - 1995 Natural Sciences and Engineering Research Council of Canada
Women's Faculty Award
1990 - 1992 Natural Sciences and Engineering Research Council of Canada
Fellowship
   
   

Courses:

MDCH 561
MDCH 571
PHAR 605
PHAR 404
PHAR 332

Select Publications:

  1. "The University of Illinois at Chicago/National Institutes of Health Center for Botanical Dietary Supplements Research for Women's Health: from plant to clinical use." Farnsworth, N. R., Krause, E. C., Bolton, J. L., Pauli, G. F., van Breemen, R. B., and Graham, J. G. Am. J. Clin. Nutr., 87, 504S-508S (2008).
  2. "High-content screening and mechanism-based evaluation of estrogenic botanical extracts." Overk, C.R., Yao, P., Chen, S., Deng, S., Imai, A., Main, M., Schinkovitz, A., Farnsworth, N.R., Pauli, G.F. and Bolton, J.L. Combinatorial Chemistry and High Throughput Screening, 11, 283 - 293 (2008).
  3. "Potential mechanisms of estrogen quinone carcinogenesis." Bolton J.L.*, Thatcher, G.R.J., Chem. Res. Toxicol., 21, 93 - 101 (2008).
  4. "Medical potential of plants used by the Q'eqchi Maya of Livingston, Guatemala for the treatment of women's health complaints." Michel, J., Duarte, R. E., Bolton, J. L., Huang, Y., Caceres, A., Veliz, M., Soejarto, D. D., Mahady, G. B., J. Ethnopharmacol., 114, 92-101 (2007).
  5. "Structural modulation of reactivity/activity in design of improved benzothiophene SERMs: Induction of chemopreventive mechanisms". Yu, B., Dietz, B., Chandrasena, E., Bolton, J.L., Thatcher, G.R.J.* Mol. Cancer Ther., 6, 2418-2428 (2007).
  6. "Uterine peroxidase catalyzed formation of di-quinone methides from the SERMs raloxifene and desmethylated arzoxifene." Liu, H., Qin, Z., Thatcher, G.R.J., Bolton, J.L.* Chem. Res. Toxicol., 20, 1676-1684 (2007).
  7. "Activation of Estrogen Receptor-Mediated Gene Transcription by the Equine Estrogen Metabolite, 4-Methoxyequilenin, in Human Breast Cancer Cells." Chang, M., Peng, K., Kastrati, I., Overk, C. R., Qin, Z., Yao, P., Bolton, J. L., and Thatcher, G. R. J.* Endocrinology, 148, 4793-4802 (2007).
  8. "Structure-activity relationships for raloxifene, arzoxifene, and a family of novel benzothiophene SERMs from in vivo and in vitro comparisons." Overk, C., Peng, K., Bolton, J.L., Thatcher, G.R.J.* Chem. Med. Chem., 2, 1520-1526 (2007).
  9. "Design and synthesis of benzothiophene SERMs with modulated oxidative activity and receptor affinity." Qin, Z., Kastrati, I., Bolton, J.L., Chandrasena, R.E.P., ,Liu, H., Petukhov, P.A., Yao, P., and Thatcher, G. R. J.* J. Med. Chem., 50, 2682-2692 (2007).
  10. "Botanical dietary supplements forum." Dietz, B., Bolton, J.L.* Chem. Res. Toxicol. (2007) 20, 586-590 (2007) (Invited Forum).
  11. "Bioactivation of selective estrogen receptor modulators (SERMs)" Dowers, T.S., Qin, Z., Thatcher, G.R.J., Bolton J.L.* Chem. Res. Toxicol. 19, 1125-1137 (2006) (Invited Review).
  12. "Response of human mammary epithelial cells to DNA damage induced by 4-hydroxyequilenin: lack of p53-mediated G1 arrest." Cuendet, M.A. and Bolton, J.L.* Chemico-Biol. Interact. 161, 271-278 (2006).
  13. "Chemical modification modulates estrogenic activity, oxidative reactivity, and metabolic stability in 4'-F-DMA, a new benzothiophene selective estrogen receptor modulator." Liu, H., Bolton, J.L. and Thatcher, G.R.J.* Chem. Res. Toxicol., 19, 779-787 (2006).
  14. "The chemical and biologic profile of a red clover (Trifolium pratense L.) phase II clinical extract." Booth, N.L., Overk, C.R., Yao, P., Burdette, J.E., Nikolic, D., Chen, S.N., Bolton, J.L., Breemen, R.B., Pauli, G.F. and Farnsworth, N.R. J. Altern. Complement. Med., 12, 133-139 (2006).
  15. "Alkaloids from Eschscholtzia californica and their capacity to inhibit binding of [3H]8-hydroxy-2-(di-N-propylamino)tetralin to 5-HT1A receptors in vitro." Gafner, S.*, Dietz, B.M., McPhail, K.L., Scott, I.M., Glinski, J.A., Russell, F.E., McCollom, M.M., Budzinski, J.W., Foster, B.C., Bergeron, C. and Bolton, J.L. J. Nat. Prod., 69, 432-435, (2006).
  16. "Serotonergic activity-guided phytochemical investigation of the roots of Angelica sinensis." Deng, S., Chen, S., Yao, P., Nikolic, D., van Breemen, R.B., Bolton, J.L., Fong, H.H.S., Farnsworth, N.R., Pauli, G.F.* J. Nat. Prod., 69, 536-541 (2006).
  17. "Seasonal Variation of Red Clover (Trifolium pratense L., Fabaceae) Isoflavones and Estrogenic Activity." Booth, N.L., Overk, C.R., Yao, P., Totura, S., Deng, Y., Hedayat, A.S., Bolton, J.L., Pauli, G.F., Farnsworth, N.R.* J. Agric. Food Chem., 54, 1277-1282 (2006).
  18. "Base selectivity and effects of sequence and DNA secondary structure on the formation of covalent adducts derived from the equine estrogen metabolite 4-hydroxyequilenin." Kolbanovskiy, A., Kuzmin, V., Shastry, A., Kolbanovskaya, M., Chen, D., Chang, M., Bolton, J.L. and Geacintov, N.E.* Chem. Res. Toxicol., 18, 1737-1747 (2005).
  19. "Screening method for the discovery of potential cancer chemoprevention agents based on mass spectrometric detection of alkylated Keap1." Liu, G., Eggler, A.L., Dietz, B.M., Mesecar, A.D., Bolton, J.L., Pezzuto, J.M., van Breemen, R.B.* Anal. Chem., 77, 6407-6414 (2005).
  20. "Analysis of protein covalent modification by xenobiotics using a covert oxidatively activated tag (COATag): Raloxifene proof of principle study." Liu, J., Li, Q., Yang, X., van Breemen, R.B., Bolton, J.L., Thatcher, G.R.J.* Chem. Res. Toxicol. 18, 1485 - 1496 (2005).
  21. "Comparison of the in vitro Estrogenic Activities of Compounds from Hops (Humulus lupulus) and Red Clover (Trifolium pretense)." Overk, C.R., Yao, P., Chadwick, L.R., Nikolic, D., Sun, Y., Cuendet, M.A., Deng, Y., Hedayat, A.S., Pauli, G.F., Farnsworth, N.R., van Breemen, R.B., and Bolton, J.L.* J. Agric. Food Chem. 53, 6246-6253 (2005). Selected for inclusion in the Annual Bibliography of Significant Advances in Dietary Supplement Research 2005.
  22. "Xanthohumol isolated from Humulus lupulus inhibits Menadione-induced DNA Damage through Induction of Quinone Reductase." Dietz, B.M., Kang, Y.H., Liu, G., Eggler, A.L., Yao, P., Chadwick, L.R., Pauli, G.F., Farnsworth, N.R., Mesecar, A.D., van Breemen, R.B., and Bolton, J.L.* Chem. Res. Toxicol. 18, 1296 – 1305 (2005) (Cover issue).
  23. "Functional and structural comparisons of cysteine residues in the Val108 wild type and Met108 variant of human soluble catechol O-methyltransferase". Li, Y., Yang, X., Chang, M., Yager, J.D., van Breemen, R. B., Bolton, J.L.* Chemico-Biol. Interact. 152, 151-163 (2005).
  24. "Characterization of two new variants of human catechol O-methyltransferase in vitro". Li, Y., Yang, X., van Breemen, R.B., Bolton, J.L.* Cancer Lett. 230, 81-89 (2005).
  25. "Estrogens and Congeners from Spent Hops (Humulus lupulus)." Chadwick, L.R., Nikolic, D., Burdette, J.E., Overk, C.R., Bolton, J.L., van Breemen, R.B., Fröhlich, R., Fong, H.H.S., Farnsworth, N.R., and Pauli, G.F.* J. Nat. Prod. 67, 2024-2032 (2005).
  26. "Bioactivation of the SERM desmethylated arzoxifene to quinoids: 4’-Fluoro substitution prevents quinoid formation." Liu, H., Liu, J., van Breemen, R. B., Thatcher, G. R. J., and Bolton, J. L.* Chem. Res. Toxicol. 18, 162-173 (2005).
  27. "Bioactivation of the SERM acolbifene to quinone methides." Liu, J., Liu, H., van Breemen, R.B., Thatcher, G. R. J., and Bolton, J. L.* Chem. Res. Toxicol. 18, 174-182 (2005).
  28. "Ultrafiltration tandem mass spectrometry of estrogens for characterization of structure and affinity for human estrogen receptors." Sun, Y., Gu, C., Liu, X., Liang, W., Yao, P., Bolton, J.L., van Breemen, R.B.* J. Am. Soc. Mass Spec. 16, 271-279 (2005).
  29. "Altered apoptotic response in MCF-10A cells treated with the equine estrogen metabolite, 4-hydroxyequilenin." Li, Y., Yao, J., Chang, M., Cuendet, M.A., and Bolton, J.L.* Toxicology Lett. 154, 225-233 (2004).
  30. "Oxidation of raloxifene to potential toxic quinoids: Formation of a di-quinone methide and o-quinones." Yu, L., Liu, H., Li, W., Zhang, F., Luckie, C., van Breemen, R.B., Thatcher, G.R.J., and Bolton, J.L.* Chem. Res. Toxicol. 17, 879-888 (2004).
  31. "Equine estrogen metabolite 4-hydroxyequilenin induces anchorage-independent growth of human mammary epithelial MCF-10A cells: differential gene expression." Cuendet, M.A., Liu, X., Pisha, E., Li, Y., Yao, J., Yu, L., and Bolton, J.L.* Mutat. Res., 550, 109-121 (2004).
  32. "Equine estrogen metabolite 4-hydroxyequilenin (4-OHEN) is a more potent inhibitor of the variant form of catechol O-methyltransferase (COMT)." Li, Y., Yoa, J., Chang, M., Yu, L., Yager, J.D., Mesecar, A.D., van Breemen, R.B., and Bolton, J.L.* Chem. Res. Toxicol. 17, 512-520 (2004).
  33. "Chemical and biological characterization and clinical evaluation of botanical dietary supplements: A phase I red clover extract as a model." Piersen, C.E., Booth, N.L., Sun, Y., Liang, W., Burdette, J.E., van Breemen, R.B., Geller, S.E., Gu, C., Banuvar, S., Shulman, L.P., Bolton, J.L. and Farnsworth, N.R.* Curr. Med. Chem. 11, 1361-1374 (2004). Cover Issue.
  34. "Quinoids formed from estrogens and antiestrogens." Bolton, J.L.*, Yu, L., and Thatcher, G.R.J. Methods Enzymol. 378, 110-123 (2004).
  35. "Isolation of linoleic acid as an estrogenic compound from the fruits of Vitex agnus-castus L. (chaste berry)." Liu, J., Burdette, J.E., Sun, Y., Deng, S., Schlecht, S.M., Zheng, W., Nikolic, D., Mahady, G.B., van Breemen, R.B., Fong, H.H.S., Pezzuto, J.M., Bolton, J.L., and Farnsworth, N.R.* Phytomedicine 11, 18-23 (2004).
  36. "Oxidation, nitration, and autoxidation of the selective estrogen receptor modulator raloxifene by nitric oxide and peroxynitrite." Toader, V., Nicolescu, A.C., Zavorin, S.I., Yu, L., Bolton, J.L., and Thatcher, G.R.J.* Chem. Res. Toxicol. 16, 1264-1276 (2003).
  37. "Black cohosh acts as a mixed competitive ligand and partial agonist of the serotonin receptor." Burdette, J. E., Liu, J., Chen, S., Fabricant, D. S., Piersen, C. E., Barker, E. L., Pezzuto, J. M., Mesecar, A., van Breemen, R. B., Farnsworth, N. R., and Bolton, J. L.* J. Agricul. Food Chem. 51, 5661-5670 (2003).
  38. "Antiestrogenic and DNA damaging effects induced by tamoxifen and toremifene metabolites." Liu, X., Pisha, E., Toretti, D. A., Yao, D., Li, Y., Yao, J., Burdette, J. E., and Bolton, J. L.*, Chem. Res. Toxicol. 16, 832-837 (2003).
  39. "Identification of novel electrophilic metabolites of piper methysticum Forst (Kava)." Johnson, B. M., Qiu, S., Zhang, S., Zhang, F., Burdette, J. E., Yu, L., Bolton, J. L., and van Breemen, R. B.* Chem. Res. Toxicol. 16, 733-740 (2003).
  40. "Effect of Halogenated Substituents on the Metabolism and Estrogenic Effects of the Equine Estrogen, Equilenin." Liu, X., Zhang, F., Liu, H., Burdette, J., Li, Y., Overk, C., Pisha, E., Yao, J., van Breemen, R. B., Swanson, S. M., and Bolton, J. L.* Chem. Res. Toxicol. 16, 741-749 (2003).
  41. "Equine catechol estrogen 4-hydroxyequilenin is a substrate and an inhibitor of catechol O-methyltransferase." Yao, J., Li, Y., Chang, M., Wu, H., Goodman, J. E., Liu, X., Liu, H., Mesecar, A. D., van Breemen, R. B., Yager, J. D., and Bolton, J. L.* Chem. Res. Toxicol. 16, 668-675 (2003).
  42. "Black cohosh protects against menadione-induced DNA damage through scavenging of reactive oxygen species: Bioassay directed isolation and characterization of compounds with antioxidant activity." Burdette, J. E., Liu, J., van Breemen, R. B., Constantinou, A. E., Pezzuto, J. M., Farnsworth, N. R., and Bolton, J. L.* J. Agricul. Food Chem. 50, 7022-7028 (2002).
  43. "A preliminary RAPD-PCR analysis of Cimicifuga species and other botanicals used for women's health." Xu, H., Fabricant, D. S., Piersen, C. E., Bolton, J. L., Pezzuto, J. M., Fong, H., Totura, S., Farnsworth, N. R., and Constantinou, A. I.* Phytomedicine 9, 566-572 (2002).
  44. "Inhibition of cellular enzymes by the equine estrogen metabolite, 4-hydroxyequilenin in human breast cancer cells: Specificity for glutathione S-transferase P1-1." Yao, J., Chang, M., Li, Y., Pisha, E., Liu, X., Yao, D., Elguindi, E. C., Blond, S. Y., and Bolton, J. L.* Chem. Res. Toxicol. 15, 935-942 (2002).
  45. "Screening drugs for metabolic stability using pulsed ultrafiltration mass spectrometry." Shin, Y. G., Bolton, J. L., and van Breemen, R. B.* Comb. Chem. High Throughput. Screen., 5, 59-64 (2002).
  46. "Oxidative DNA damage induced by equine estrogen metabolites: Role of estrogen receptor alpha" Liu, X., Yao, J., Pisha, E., Hua, Y., van Breemen, R. B., and Bolton, J. L.* Chem. Res. Toxicol. 15, 512-519 (2002).
  47. "Quinoids, quinoids radicals, and phenoxyl radicals from estrogens and antiestrogens: Role in carcinogenesis?" Bolton, J. L.* Toxicology 177, 55-65 (2002) (Invited Review).
  48. "In vivo estrogenic effects of Trifolium pratense (red clover) in ovariectomized sprague-dawley rats." Burdette, J. E., Liu, J., Lantvit, D., Lim, E., Booth, N., Bhat, K. P. L., van Breemen, R. B., Constantinou, A. I., Pezzuto, J. M., Farnsworth, N. R., and Bolton, J. L.*, J. Nutrition 132, 27-30 (2002).
  49. "4-Hydroxyequilenin induces DNA damage in the rat mammary gland: Formation of single strand breaks, apurinic sites, stable adducts, and oxidized bases." Zhang, F., Swanson, S., van Breemen, R. B., Hua, Y., Liu, X. and Bolton, J. L.* Chem. Res. Toxicol. 14, 1654-1659 (2001).
  50. "Synthesis and reactivity of potential toxic metabolites of tamoxifen analogues: Droloxifene- and Toremifene-o-quinones." Yao, D., Zhang, F., Yu, L., Yang, Y., van Breemen, R.B., and Bolton, J. L.* Chem. Res. Toxicol. 14, 1643-1653 (2001).
  51. "Screening botanical extracts for quinoid metabolites." Johnson, B. M., Bolton, J. L. and van Breemen, R. B.* Chem. Res. Toxicol. 14, 1546-1551 (2001).
  52. "Synthesis and reactivity of catechol metabolites from 8,9-dehydroestrone." Zhang, F., Yao, D., Hua, Y., van Breemen, R.B., Bolton, J.L.*, Chem. Res. Toxicol., 14, 754-763 (2001).
  53. "Metabolism of equilenin in human breast cancer cells. Role of cytochrome P4501A1 and 1B1." Spink, D. C.*, Zhang, F., Husain, M. M., Katz, B. H., Liu, X. and Bolton, J. L.* Chem. Res. Toxicol., 14, 572-581 (2001).
  54. "Bioactivation of tamoxifen to metabolite E quinone methide: reaction with glutathione and DNA." Fan, P.W. and Bolton, J.L.*, Drug Metabolism and Disposition, 29, 891-896 (2001).
  55. "Evaluation of the estrogenic potency of plant extracts for the potential treatment of menopausal symptoms." Liu, J., Burdette, J., Constantinou, A.I, Pezzuto, J.M., Farnsworth, N., van Breemen, R.B., Booth, N., Bolton, J.L.*, J. Agricultural Food Chem., 49, 2472-2479 (2001).
  56. "Structural and functional consequences of 4-hydroxyequilenin-o-quinone mediated inactivation of human glutathione S-transferase Pi." Chang, M., Shin, Y.G., van Breemen, R.B., Blond, S.Y., Bolton, J.L.*, Biochemistry, 40, 4811-4820 (2001).
  57. "Evidence that a metabolite of equine estrogens, 4-hydroxyequilenin, induces cellular transformation in vitro." Pisha, E., Liu, X., Constantinou, A. I., Bolton, J. L.*, Chem. Res. Toxicol., 14, 82-90 (2001).
  58. "Comparison of negative and positive ion electrospray tandem mass spectrometry for the LC-MS-MS analysis of oxidized deoxynucleosides." Hua, Y., Wainhaus, S. B., Yang, Y., Shen, L., Xiong, Y., Xu, X., Zhang, F., Bolton, J. L. and van Breemen, R. B.* J. Am. Soc. Mass Spectrometry, 12, 80-87 (2000).
  59. "Selection of cancer chemopreventive agents based on inhibition of topoisomerase II activity." Cho, K. H., Pezzuto J. M., Bolton J. L., Steele V.E., Kelloff G. J., Lee S. K., Constantinou, A.*, European J. Cancer, 36, 2146-2156 (2000).
  60. "A metabolite of equine estrogens, 4-hydroxyequilenin induces DNA damage and apoptosis in breast cancer cell lines." Chen, Y., Liu, X, Pisha, E., Constantinou, A.I., Hua, Y., Shen, L., van Breemen, R.B., Elguindi, E.C., Blond, S.Y., Zhang, F., Bolton, J.L.*, Chem. Res. Toxicol., 13, 342-350 (2000).
  61. "Role of quinones in toxicology." Bolton, J. L.*, Trush, M. A., Penning, T. M., Dryhurst, G. and Monks, T. J., Chem. Res. Toxicol., 13, 135-160 (2000), Invited review, March Cover Issue.
  62. "4-Hyroxylated metabolites of the antiestrogens tamoxifen and toremifene are metabolized to unusually stable quinone methide." Fan, P., Zhang, F., Bolton, J.L.*, Chem. Res. Toxicol., 13, 45-52 (2000).
  63. "Synthesis and reactivity of a potential carcinogenic metabolite of tamoxifen: 3,4-Dihydroxytamoxifen-o-quinone." Zhang, F., Fan, P., Liu, X., Shen, L., van Breemen, R.B., Bolton J.L.*, Chem. Res. Toxicol., 13, 53-62 (2000).
  64. 64. "Expression and purification of hexahistidine-tagged human glutathione S-transferase in Escherichia coli." Chang, M., Bolton, J. L. and Blond, S. Y.*, Protein Expression and Purification, 17 443-448 (1999).
  65. "Screening for xenobiotic electrophilic metabolites using pulsed ultrafiltration mass- spectrometry. " Nikolic, D., Fan, P. W., Bolton, J. L. and van Breemen, R. B*., Combinatorial Chemistry and High Throughput Screening, 2 165-175 (1999).
  66. "Synthesis of the equine estrogen metabolites 2-hydroxyequilin and 2-hydroxyequilenin." Zhang, F. and Bolton, J. L.* Chem. Res. Toxicol., 12 200-203 (1999).
  67. 67. "The major metabolite of equilin, 4-hydroxyequilin autoxidizes to an o-quinone which isomerizes to the potent cytotoxin 4-hydroxyequilenin-o-quinone." Zhang, F., Chen, Y., Pisha, E., Shen, L., Xiong, Y., van Breemen, R. B. and Bolton, J. L.* Chem. Res. Toxicol., 12 204-213 (1999).
  68. 68. "Lifetime and reactivity of an ultimate tamoxifen carcinogen: The tamoxifen carbocation." Sanchez, C., Shibutani, S., Dasaradhi, L., Bolton, J.L., Fan, P. W. and McClelland, R. A.*, J. Am. Chem. Soc., 120, 13513-13514 (1998).
  69. "Role of quinoids in hormonal carcinogenesis." Bolton, J. L.*, Pisha, E., Zhang, F., and Qiu, S. Chem. Res. Toxicol., 11, 1113-1127 (1998) Invited review, October Cover Issue.
  70. "The equine estrogen metabolite 4-hydroxyequilenin causes DNA single strand breaks and oxidation of DNA bases in vitro.", Chen, Y., Shen, L., Zhang, F., Lau, S., van Breemen, R.B., Nikolic, D., Bolton, J.L.*, Chem. Res. Toxicol., 11, 1105-1111 (1998).
  71. "Inhibition of glutathione S-transferase activity by the quinoid metabolites of equine estrogens." Chang, M., Zhang, F., Shen, L., Pauss, N., Alam, I., van Breemen, R. B., Blond, S.Y., and Bolton, J. L.*, Chem. Res. Toxicol., 11, 758-765 (1998).
  72. "Laccase and not tyrosinase is the enzyme responsible for quinone methide production from 2,6-dimethoxy-4-allylphenol." Sugumaran, M.* and Bolton, J.L., Arch. Biochem. Biophys., 353, 207-212 (1998).
  73. "Alkylation of 2'-deoxynucleosides and DNA by the Premarin metabolite, 4-hydroxyequilenin semiquinone radical." Shen, L., Qiu, S., Chen, Y., Zhang, F., van Breemen, R. B., Nikolic, D. and Bolton, J. L.*, Chem. Res. Toxicol., 11, 94-101 (1998). February Cover Issue. C&E News, Feb. 16, 1998, pp. 32.
  74. "Metabolic screening using on-line ultrafiltration mass spectrometry." van Breemen, R. B.*, Nikolic, D. and Bolton, J. L., Drug Metab. Dispos., 26, 85-90 (1998).
  75. "Reaction of the Premarin® metabolite 4-hydroxyequilenin semiquinone radical with 2'-deoxyguanosine: Formation of unusual cyclic adducts." Shen, L., Qiu S., van Breemen, R. B., Zhang, F., Chen, Y. and Bolton, J. L.*, J. Am. Chem. Soc., 119, 11126-11127 (1997).
  76. "Influence of quinone methide reactivity on the alkylation of thiol and amino groups in proteins: studies utilizing amino acid and peptide models." Bolton, J. L., Turnipseed, S. B. and Thompson, J. A.*, Chem.-Biol. Interact., 107, 185-200 (1997).
  77. "The reactivity of o-quinones which do not isomerize to quinone methides correlates with alkycatechol-induced toxicity in human melanoma cells." Bolton, J. L.*, Pisha, E., Shen, L., Krol, E. S., Iverson, S. L., Huang, Z., van Breemen, R. B. and Pezzuto, J. M., Chem.-Biol. Interact., 106, 133-148 (1997).
  78. "Oxo-substituents markedly alter the phase II metabolism of ?-hydroxybutenylbenzenes: Models probing the bioactivation mechanisms of tamoxifen." Ramakrishna, K. V., Fan, P., Boyer, C. S., Dalvie, D. and Bolton, J. L.*, Chem. Res. Toxicol., 10, 887-894 (1997).
  79. "Oxidation of 4-alkylphenols and catechols by tyrosinase: ortho-Substituents alter the mechanism of quinoid formation." Krol, E. S. and Bolton, J. L.*, Chem.-Biol. Interact., 104, 11-27 (1997).
  80. "Bioreductive activation of catechol estrogen-ortho-quinones: Aromatization of the B ring in 4-hydroxyequilenin markedly alters quinoid formation and reactivity." Shen, L., Pisha, E., Huang, Z., Pezzuto, J. M., Krol, E., Alam, Z., van Breemen, R. B., and Bolton, J. L.*, Carcinogenesis, 18, 1093-1101 (1997).
  81. "Covalent modification of proteins and peptides by the quinone methide from 2-tert-Butyl-4,6-dimethylphenol: Selectivity and reactivity with respect to competitive hydrolysis." McCracken, P.G., Bolton, J.L.*, Thatcher, G.R.J.*, J. Org. Chem., 62, 1820-1825 (1997).
  82. "Alkylation of 2`-Deoxynucleosides and DNA by Quinone Methides Derived from 2,6-Di-tert-butyl-4-methylphenol." Lewis, M. A., Graff, D. A., Bolton, J. L., and Thompson, J. A.*, Chem. Res. Toxicol., 9, 1368-1374 (1996).
  83. "p-Quinone methides are the major decomposition products of catechol estrogen o-quinones." Judy L. Bolton* and Li Shen, Carcinogenesis, 17, 925-929 (1996). Accelerated Paper.
  84. "CYP2E1-dependent bioactivation of 1,1-dichloroethylene in murine lung: Formation of reactive intermediates and glutathione conjugates." Dowsley, T. F., Ulreich, J. B., Bolton, J. L., Park, S. S. and Forkert, P. G.*, Toxicol. Appl. Pharmacol., 139, 42-48 (1996).
  85. "Bioactivation of estrone and its catechol metabolites to quinoid-glutathione conjugates in rat liver microsomes." Suzanne L. Iverson, Li Shen, Nilgun Anlar, and Judy L. Bolton*, Chem. Res. Toxicol., 9, 492-499 (1996).
  86. "Mechanism of isomerization of 4-propyl-o-quinone to its tautomeric p-quinone methide." Judy L. Bolton*, Hao Ming Wu, and Li Qing Hu, Chem. Res. Toxicol., 9, 109-113 (1996).
  87. "Direct evidence for o-quinone - p-quinone methide tautomerism during tyrosinase catalyzed oxidation of 4-allylcatechol." Manickam Sugumaran* and Judy L. Bolton, Biochem. Biophys. Res. Commun., 213, 469-474 (1995).
  88. " The influence of the para-alkyl substituent on the isomerization of o-quinones to p-quinone methides: Potential bioactivation mechanism for catechols." Suzanne L. Iverson, Li Qing Hu, Vesna Vukomanovic, Judy L. Bolton*, Chem. Res. Toxicol., 8, 537-544 (1995).
  89. "o-Methoxy-4-alkylphenols that form quinone methides of intermediate reactivity are the most toxic in rat liver slices." David C. Thompson*, Kumar Perera, E.S. Krol, Judy L. Bolton* Chem. Res. Toxicol., 8, 323 - 327 (1995).
  90. "The influence of 4-alkyl substituents on the formation and reactivity of 2-methoxy-quinone methides: Evidence that extended ?-conjugation dramatically stabilizes the quinone methide formed from eugenol." Judy L. Bolton*, Ellen Comeau, Vesna Vukomanovic, Chem.-Biol. Interact., 95, 279-290 (1995).
  91. "Reaction of glutathione with the electrophilic metabolites of 1,1-dichloroethylene" Taylor F. Dowsley, Poh G. Forkert, Lisbeth A. Benesch, Judy L. Bolton*, Chem.-Biol. Interact., 95, 227-244 (1995).
  92. "Evidence that 4-allyl-ortho-quinones spontaneously rearrange to their more electrophilic quinone methides: Potential bioactivation mechanism for the hepatocarcinogen safrole" Judy L. Bolton*, Nick M. Acay, Vesna Vukomanovic, Chem. Res. Toxicol., 7, 443-450 (1994).
  93. "Reaction of quinone methides with proteins: Analysis of myoglobin adduct formation by electrospray mass spectrometry." Judy L. Bolton*, J.C.Y. Le Blanc, K.W.M. Siu, Biological Mass Spectrometry, 22, 666-668 (1993).
  94. "Metabolic activation of the tumor promoting agent butylated hydroxytoluene by mouse bronchiolar Clara cells." Judy L. Bolton, John A. Thompson*, Alban J. Allentoff, Alvin, M. Malkinson Toxicol. Appl. Pharmacol., 123, 43-49 (1993).
  95. "Heterolytic versus homolytic peroxide bond cleavage by sperm whale myoglobin and myoglobin mutants." Alban J. Allentoff, Judy L. Bolton, Angela Wilks, John A. Thompson*, and Paul R. Ortiz de Montellano*, J. Am. Chem. Soc., 114, 9744-9749 (1992).
  96. "The enzymatic formation and chemical reactivity of quinone methides correlate with alkylphenol-induced toxicity in rat hepatocytes." Judy L. Bolton, Louis G.J. Valerio, John A. Thompson*, Chem. Res. Toxicol., 5, 816-822 (1992).
  97. "Oxidation of Butylated Hydroxytoluene to toxic metabolites: Factors influencing hydroxylation and quinone methide formation by hepatic and pulmonary microsomes." Judy L. Bolton and John A. Thompson*, Drug Metabolism and Disposition 19, 467-472 (1991).
  98. "Relationship between the Metabolism of Butylated Hydroxytoluene (BHT) and lung tumor promotion in Mice" John A. Thompson*, Judy L. Bolton, Alvin M. Malkinson, Experimental Lung Research 17, 439-453 (1991).
  99. "Formation and Reactivity of Alternative Quinone Methides From Butylated Hydroxytoluene: A Possible Explanation for Species-Specific Pneumotoxicity." Judy L. Bolton, Hubert Sevestre, Basil O. Ibe, John A. Thompson*, Chem. Res. Toxicol. 3, 65-70, (1990).
  100. "Kinetics and Mechanism of the Decomposition in Aqueous Solutions of 2-hydroxyl-aminoimidazoles." Judy L. Bolton and Robert A. McClelland*, J. Am. Chem. Soc. 111, 8172-8181, (1989).
  101. "Azide Ion Trapping and Lifetime in Aqueous Solution of a Primary Carbenium Ion Stabilized by a 2-Imidazoyl ring." Judy L. Bolton and Robert A. McClelland*, Canadian Journal of Chemistry 67, 1139-1143, (1989).
  102. "Experimental and Theoretical Investigation of C-Nitroso Rotation in 2-Nitrosoimidazoles." Judy L. Bolton, M.R. Peterson, R.A. McClelland*, Canadian Journal of Chemistry 66, 3044-3049, (1988).
  103. "Theoretical Studies of Imidazole Nitrenium and Carbenium Ions." Judy L. Bolton, Robert A. McClelland*, Journal of Molecular Structure (Theochem) 165, 379-389, (1988).
  104. "Relative Reactivities of Heteraromatic Cations towards Reduction by 1,4-Dihydro-nicotinamides." John W. Bunting* and Judy L. Bolton, Tetrahedron 42, 1007-1019, (1986).

Book Chapters:

  1. "Estrogenic activity of the equine estrogen metabolite, 4-methoxyequilenin." Chang, M., Overk, C. R., Kastrati, I., Peng, K., Yao, P., Qin, Z., Petukhov, P., Bolton, J. L., and Thatcher, G. R. J.* (2007), in Hormonal Carcinogenesis V (Li, J. J., Li, S. A., and Llombart-Bosch, A., Eds.) pp 579-583, Springer, New York.
  2. "Bioactivation of estrogens to toxic quinones." Bolton, J.L.* In Advances in Molecular Toxicology, 1, 1-23 (2006).
  3. "Evidence-based herbal medicine: Challenges in efficacy and safety assessments." Fong, H.H.S., Pauli, G.F., Bolton, J.L., van Breemen, R.B., Banuvar, S., Shulman, L., Geller, S.E. and Farnsworth, N.R. (2006) In: Leung, P.C., Fong, H., Xue, C.C., Eds., Current Review of Chinese Medicine, 2, 11-26 (2006).
  4. "Quinoids as reactive intermediates in estrogen carcinogenesis." Bolton, J. L.*, Chang, M., In: Snyder, R., Kocsis, J. J., Jollow, D. J, Witmer, C. M., Sipes, I. G., Eds., Sixth Symposium on Biological Reactive Intermediates, Molecular and Cellular Effects and Human Impact. New York, Plenum Press, 497-507 (2001).
  5. "Bioactivation of 2,6-di-tert-butyl-4-methyl phenol (BHT) and hydroxylated analogs to toxic quinoid metabolites." John A. Thompson*, Judy L. Bolton, Kathleen M. Schullek and Hubert Sevestre. In: Snyder R, Kocsis JJ, Jollow DJ, Witmer, CM, Sipes IG, eds., Fourth Symposium on Biological Reactive Intermediates, Molecular and Cellular Effects and Human Impact. New York, Plenum Press, 393-398 (1991).

 

---