Areas of expertise
Toxicology , Aromatase (CYP19) , Cytochrome P450 , Endocrine disruptors , Natural compounds , Pesticides , Steroidogenesis
Certain pesticides, environmental contaminants, (veterinary and human) drugs and compounds of natural origin can interfere with steroid biosynthesis and metabolism in humans and wildlife. The mechanisms of deregulation of steroidogenesis by chemicals and the toxicological consequences thereof are relatively unexplored fields of research, yet are currently of great interest given the concern regarding hormone-disrupting chemicals, the rise in hormone-dependent cancers and the increased incidence of reproductive problems in humans and wildlife.
My current research is focused on the synthesis and metabolism of estrogens and androgens by various cytochrome P450 and reductase enzymes that are present in steroidogenic tissues and hormone-dependent tumors. Enzymes such as CYP19 (aromatase), CYP17 and 5α-reductase, among others are of particular interest because their elevated expression is associated with an increased risk of some cancers.
My emphasisis on how chemicals disrupt the expression or catalytic activity of steroidogenic enzymes in vitro in various mammalian cell lines, and in vivo in transgenic mice. Induction by xenobiotics appears to be mediated by the cAMP-activated protein kinase A pathway in gonads and adrenocortical cells (Sanderson et al. 2004). However, in other target tissues other second messenger systems (PKC, Jak/Stat, glucocorticoids) are involved (Heneweer et al. 2004). This work will be expanded to study primary cells from human and wildlife tissues.
Various plant products are known to interfere with steroidogenesis and/or metabolism and to act as agonists or antagonists for estrogen and androgen receptors. However, for many of these compounds, the specific target enzymes or hormone receptors are unknown. As part of a long-term project funded by NSERC, the (steroidogenic) enzyme inhibiting or inducing properties of various naturally occurring polyphenolic compounds and synthetic analogues of these compounds will be examined and structure-activity relationships will be delineated.
Effects of chemicals on in vitro steroid synthesis are highly cell-type dependent and do not take into account biokinetics factors such as absorption, distribution and metabolism. Limited numbers of in vivo studies will be performed to confirm in vitro findings and to validate cell-based bioassays as useful and predictive models for effects in vivo.
J. Thomas Sanderson obtained his B.Sc. (Faculty of Chemistry and Pharmacochemistry, 1989) from the Free University of Amsterdam, The Netherlands, followed by a Ph.D. (Faculty of Pharmaceutical Sciences, 1994) from the University of British Columbia in Vancouver, Canada. After a postdoctoral research position at Michigan State University (National Food Safety and Toxicology Center, 1994-1997), he held an Assistant Professorship at Utrecht University, The Netherlands (Institute for Risk Assessment Sciences, 1997-2005) where he was tenured since 2003. Since 2005, Thomas Sanderson holds a position of Associate Professor at the INRS-Institute Armand-Frappier
His research interests concern the interactions of chemicals with the expression and function of enzymes involved in steroid biosynthesis, and their relation to the development of hormone-dependent cancers and endocrine disruption. Current research activities, funded by the Natural Sciences and Engineering Research Council of Canada (NSERC) aim to elucidate the mechanism by which a wide variety of chemicals, including environmental contaminants, drugs and compounds of natural origin interfere with androgen and estrogen biosynthesis in human and animal models.
CARON-BEAUDOIN, E., DENISON, M. S. & SANDERSON, J. T. (2015)
Effects of neonicotinoids on promoter-specific expression and activity of aromatase (CYP19) in human adrenocortical carcinoma (H295R) and primary umbilical vein endothelial (HUVEC) cells,
SANDERSON, J. T. (2015)
Disruptors of Androgen Action and Synthesis.
Endocrine Disruption and Human Health. 76-90.
GOLDBERG, A. A., DRAZ, H., MONTES-GRAJALES, D., OLIVERO-VERBEL, J., SAFE, S. H. & SANDERSON, J. T. (2015)
3,3′-Diindolylmethane (DIM) and its ring-substituted halogenated analogs (ring-DIMs) induce differential mechanisms of survival and death in androgen-dependent and -independent prostate cancer cells,
Genes Cancer, 6, 5-6, 265-80.
ROBITAILLE, C. N., RIVEST, P. & SANDERSON, J. T. (2015)
Antiandrogenic Mechanisms of Pesticides in Human LNCaP Prostate and H295R Adrenocortical Carcinoma Cells,
Toxicological Sciences, 143, 1, 126-35.
GOODSON, W. H., 3RD, LOWE, L., CARPENTER, D. O., GILBERTSON, M., MANAF ALI, A., LOPEZ DE CERAIN SALSAMENDI, A., LASFAR, A., CARNERO, A., AZQUETA, A., AMEDEI, A., CHARLES, A. K., COLLINS, A. R., WARD, A., SALZBERG, A. C., COLACCI, A., OLSEN, A. K., BERG, A., BARCLAY, B. J., ZHOU, B. P., BLANCO-APARICIO, C., BAGLOLE, C. J., DONG, C., MONDELLO, C., HSU, C. W., NAUS, C. C., YEDJOU, C., CURRAN, C. S., LAIRD, D. W., KOCH, D. C., CARLIN, D. J., FELSHER, D. W., ROY, D., BROWN, D. G., RATOVITSKI, E., RYAN, E. P., CORSINI, E., ROJAS, E., MOON, E. Y., LACONI, E., MARONGIU, F., AL-MULLA, F., CHIARADONNA, F., DARROUDI, F., MARTIN, F. L., VAN SCHOOTEN, F. J., GOLDBERG, G. S., WAGEMAKER, G., NANGAMI, G., CALAF, G. M., WILLIAMS, G., WOLF, G. T., KOPPEN, G., BRUNBORG, G., KIM LYERLY, H., KRISHNAN, H., AB HAMID, H., YASAEI, H., SONE, H., KONDOH, H., SALEM, H. K., HSU, H. Y., PARK, H. H., KOTURBASH, I., MIOUSSE, I. R., SCOVASSI, A. I., KLAUNIG, J. E., VONDRACEK, J., RAJU, J., ROMAN, J., WISE, J. P., SR., WHITFIELD, J. R., WOODRICK, J., CHRISTOPHER, J. A., OCHIENG, J., MARTINEZ-LEAL, J. F., WEISZ, J., KRAVCHENKO, J., SUN, J., PRUDHOMME, K. R., NARAYANAN, K. B., COHEN-SOLAL, K. A., MOORWOOD, K., GONZALEZ, L., SOUCEK, L., JIAN, L., D’ABRONZO, L. S., LIN, L. T., LI, L., GULLIVER, L., MCCAWLEY, L. J., MEMEO, L., VERMEULEN, L., LEYNS, L., ZHANG, L., VALVERDE, M., KHATAMI, M., ROMANO, M. F., CHAPELLIER, M., WILLIAMS, M. A., WADE, M., et al. (2015)
Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead,
Carcinogenesis, 36 Suppl 1, S254-96.
ENGSTROM, W., DARBRE, P., ERIKSSON, S., GULLIVER, L., HULTMAN, T., KARAMOUZIS, M. V., KLAUNIG, J. E., MEHTA, R., MOORWOOD, K., SANDERSON, T., SONE, H., VADGAMA, P., WAGEMAKER, G., WARD, A., SINGH, N., AL-MULLA, F., AL-TEMAIMI, R., AMEDEI, A., COLACCI, A. M., VACCARI, M., MONDELLO, C., SCOVASSI, A. I., RAJU, J., HAMID, R. A., MEMEO, L., FORTE, S., ROY, R., WOODRICK, J., SALEM, H. K., RYAN, E., BROWN, D. G. & BISSON, W. H. (2015)
The potential for chemical mixtures from the environment to enable the cancer hallmark of sustained proliferative signalling,
Carcinogenesis, 36 Suppl 1, S38-60.
THIBEAULT, A. A., DEROY, K., VAILLANCOURT, C. & SANDERSON, J. T. (2014)
A Unique Co-culture Model for Fundamental and Applied Studies of Human Fetoplacental Steroidogenesis and Interference by Environmental Chemicals,
Environmental Health Perspectives, 122, 4, 371-7.
GOLDBERG, A. A., TITORENKO, V. I., BEACH, A., ABDELBAQI, K., SAFE, S. & SANDERSON, J. T. (2014)
Ring-substituted analogs of 3,3′-diindolylmethane (DIM) induce apoptosis and necrosis in androgen-dependent and -independent prostate cancer cells,
Investigational New Drugs, 32, 1, 25-36.
SANDERSON, J. T., CLABAULT, H., PATTON, C., LASSALLE-CLAUX, G., JEAN-FRANCOIS, J., PARÉ, A. F., HÉBERT, M. J., SURETTE, M. E. & TOUAIBIA, M. (2013)
Antiproliferative, antiandrogenic and cytotoxic effects of novel caffeic acid derivatives in LNCaP human androgen-dependent prostate cancer cells,
Bioorganic and Medicinal Chemistry, 21, 22, 7182-93.
GOLDBERG, A. A., TITORENKO, V. I., BEACH, A. & SANDERSON, J. T. (2013)
Bile acids induce apoptosis selectively in androgen-dependent and -independent prostate cancer cells,
PeerJ, 1, e122.
GASMI, J. & SANDERSON, J. T. (2013)
Jacaric acid and its octadecatrienoic acid geoisomers induce apoptosis selectively in cancerous human prostate cells: a mechanistic and 3-D structure-activity study,
Phytomedicine, 20, 8-9, 734-42.
RIVEST, P., RENAUD, M. & SANDERSON, J. T. (2011)
Proliferative and androgenic effects of indirubin derivatives in LNCaP human prostate cancer cells at sub-apoptotic concentrations,
Chemico-Biological Interactions, 189, 3, 177-185.
KLEMPAN, T., HUDON-THIBEAULT, A. A., OUFKIR, T., VAILLANCOURT, C. & SANDERSON, J. T. (2011)
Stimulation of serotonergic 5-HT(2A) receptor signaling increases placental aromatase (CYP19) activity and expression in BeWo and JEG-3 human choriocarcinoma cells,
Placenta, 32, 9, 651-656.
ABDELBAQI, K., LACK, N., GUNS, E. T., KOTHA, L., SAFE, S. & SANDERSON, J. T. (2011)
Antiandrogenic and growth inhibitory effects of ring-substituted analogs of 3,3′-diindolylmethane (ring-DIMs) in hormone-responsive LNCaP human prostate cancer cells,
Prostate, 71, 13, 1401-12.
RIVEST, P., DEVINE, P. J. & SANDERSON, J. T. (2010)
Evaluation of a bioluminescent mouse model expressing aromatase PII-promoter-controlled luciferase as a tool for the study of endocrine disrupting chemicals,
Toxicology and Applied Pharmacology, 249, 1, 33-40.
OUFKIR, T., ARSENEAULT, M., SANDERSON, J. T. & VAILLANCOURT, C. (2010)
The 5-HT2A serotonin receptor enhances cell viability, affects cell cycle progression and activates MEK-ERK1/2 and JAK2-STAT3 signalling pathways in human choriocarcinoma cell lines,
Placenta, 31, 5, 439-447.
GASMI, J. & SANDERSON, J. T. (2010)
Growth inhibitory, antiandrogenic, and pro-apoptotic effects of punicic acid in LNCaP human prostate cancer cells,
Journal of Agricultural and Food Chemistry, 58, 23, 12149-12156.
SANDERSON, J. T. (2009)
Placental and fetal steroidogenesis,
Methods in molecular biology (Clifton, N.J.), 550, 127-136.
SINGH, M., ARSENEAULT, M., SANDERSON, T., MURTHY, V. & RAMASSAMY, C. (2008)
Challenges for research on polyphenols from foods in Alzheimer’s disease: Bioavailability, metabolism, and cellular and molecular mechanisms,
Journal of Agricultural and Food Chemistry, 56, 13, 4855-4873.
SANDERSON, T., RENAUD, M., SCHOLTEN, D., NIJMEIJER, S., VAN DEN BERG, M., COWELL, S., GUNS, E., NELSON, C., MUTARAPAT, T. & RUCHIRAWAT, S. (2008)
Effects of lactone derivatives on aromatase (CYP19) activity in H295R human adrenocortical and (anti)androgenicity in transfected LNCaP human prostate cancer cells,
European Journal of Pharmacology, 593, 1-3, 92-98.
VAN MEEUWEN, J. A., VAN DEN BERG, M., SANDERSON, J. T., VERHOEF, A. & PIERSMA, A. H. (2007)
Estrogenic effects of mixtures of phyto- and synthetic chemicals on uterine growth of prepubertal rats,
Toxicology Letters, 170, 2, 165-76.
VAN MEEUWEN, J. A., TER BURG, W., PIERSMA, A. H., VAN DEN BERG, M. & SANDERSON, J. T. (2007)
Mixture effects of estrogenic compounds on proliferation and pS2 expression of MCF-7 human breast cancer cells,
Food and Chemical Toxicology, 45, 11, 2319-2330.
HECKER, M., SANDERSON, J. T. & KARBE, L. (2007)
Suppression of aromatase activity in populations of bream (Abramis brama) from the river Elbe, Germany,
Chemosphere, 66, 3, 542-52.
SANDERSON, T. (2006)
Pesticides and the disruption of the enzyme aromatase,
Outlooks on Pest Management, 17, 1, 21-23.
SANDERSON, J. T. (2006)
The steroid hormone biosynthesis pathway as a target for endocrine-disrupting chemicals,
Toxicological Sciences, 94, 1, 3-21.
PETERS, A. K., SANDERSON, J. T., BERGMAN, A. & VAN DEN BERG, M. (2006)
Antagonism of TCDD-induced ethoxyresorufin-O-deethylation activity by polybrominated diphenyl ethers (PBDEs) in primary cynomolgus monkey (Macaca fascicularis) hepatocytes,
Toxicology Letters, 164, 2, 123-132.
GRACIA, T., HILSCHEROVA, K., JONES, P. D., NEWSTED, J. L., ZHANG, X., HECKER, M., HIGLEY, E. B., SANDERSON, J. T., YU, R. M. K., WU, R. S. S. & GIESY, J. P. (2006)
The H295R system for evaluation of endocrine-disrupting effects,
Ecotoxicology and Environmental Safety, 65, 3, 293-305.
CANTOÌN, R. F., SANDERSON, J. T., NIJMEIJER, S., BERGMAN, A., LETCHER, R. J. & VAN DEN BERG, M. (2006)
In vitro effects of brominated flame retardants and metabolites on CYP17 catalytic activity: A novel mechanism of action?,
Toxicology and Applied Pharmacology, 216, 2, 274-281.
RANKOUHI, T. R., KOOMEN, B., SANDERSON, J. T., BOSVELD, A. T., SEINEN, W. & VAN DEN BERG, M. (2005)
Induction of ethoxy-resorufin-O-deethylase activity by halogenated aromatic hydrocarbons and polycyclic aromatic hydrocarbons in primary hepatocytes of the green frog (Rana esculenta),
Environmental Toxicology and Chemistry, 24, 6, 1428-35.
LETCHER, R. J., SANDERSON, J. T., BOKKERS, A., GIESY, J. P. & VAN DEN BERG, M. (2005)
Effects of bisphenol A-related diphenylalkanes on vitellogenin production in male carp (Cyprinus carpio) hepatocytes and aromatase (CYP19) activity in human H295R adrenocortical carcinoma cells,
Toxicology and Applied Pharmacology, 209, 2, 95-104.
HENEWEER, M., VAN DEN BERG, M., DE GEEST, M. C., DE JONG, P. C., BERGMAN, A. & SANDERSON, J. T. (2005)
Inhibition of aromatase activity by methyl sulfonyl PCB metabolites in primary culture of human mammary fibroblasts,
Toxicology and Applied Pharmacology, 202, 1, 50-8.
HENEWEER, M., MUUSSE, M., VAN DEN BERG, M. & SANDERSON, J. T. (2005)
Additive estrogenic effects of mixtures of frequently used UV filters on pS2-gene transcription in MCF-7 cells,
Toxicology and Applied Pharmacology, 208, 2, 170-7.
CANTOÌN, R. F., SANDERSON, J. T., LETCHER, R. J., BERGMAN, A. & VAN DEN BERG, M. (2005)
Inhibition and induction of aromatase (CYP19) activity by brominated flame retardants in H295R human adrenocortical carcinoma cells,
Toxicological Sciences, 88, 2, 447-455.
HENEWEER, M., MUUSSE, M., DINGEMANS, M., DE JONG, P. C., VAN DEN BERG, M. & SANDERSON, J. T. (2005)
Co-culture of primary human mammary fibroblasts and MCF-7 cells as an in vitro breast cancer model,
Toxicological Sciences, 83, 2, 257-63.
Van Duursen, M.B., J.T. Sanderson, P.C. De Jong, M. Kraaij, and M. Van Den Berg (2004)
Phytochemicals inhibit catechol-o-methyltransferase activity in cytosolic fractions from healthy human mammary tissues: implications for catechol estrogen-induced DNA damage.
Toxicol. Sci. 81: 316-324 .
Van Duursen, M., J.T. Sanderson, M. van der Bruggen, J. van der Linden, and M. van den Berg (2003)
Effects of several dioxin-like compounds on estrogen metabolism in the malignant MCF-7 and nontumorigenic MCF-10A human mammary epithelial cell lines.
Toxicol. Appl. Pharmacol. 190: 241-250 .
Sanderson, J. T., J. Jordijk, J., M.S. Denison, M.F. Springsteel, M.H. Nantz, and M. Van Den Berg (2004)
Induction and Inhibition of aromatase (CYP19) activity by natural and synthetic flavonoid compounds in H295R human adrenocortical carcinoma cells.
Toxicol. Sci. 82 : 70-79.
Sanderson, J.T., J. Boerma, G.W. Lansbergen, and M. van den Berg. (2002)
Induction and inhibition of aromatase (CYP19) activity by various classes of pesticides in H295R human adrenocortical carcinoma cells.
Toxicol. Appl. Pharmacol. 182: 44-54.
Sanderson, J.T., L. Slobbe, G.W. Lansbergen, S. Safe, and M. van den Berg (2001)
2,3,7,8-Tetrachlorodibenzo-p-dioxin and diindolylmethanes differentially induce cytochrome P450 1A1, 1B1, and 19 in H295R human adrenocortical carcinoma cells.
Toxicol. Sci. 6 1: 40-48.
Sanderson, J.T., R.J. Letcher, M. Heneweer, J.P. Giesy, and M. van den Berg (2001)
Effects of chloro-s-triazine herbicides and metabolites on aromatase activity in various human cell lines and on vitellogenin production in male carp hepatocytes.
Environ. Health Perspect. 109: 1027-1031.
Sanderson, J.T., W. Seinen, J.P. Giesy, and M. van den Berg (2000)
2-Chloro-s-triazine herbicides induce aromatase (CYP19) activity in H295R human adrenocortical carcinoma cells: a novel mechanism for estrogenicity?
Toxicol. Sci. 54: 121-127.
Sanderson, J.T., J.M. Aarts, A. Brouwer, K.L. Froese, M.S. Denison, and J.P. Giesy (1996)
Comparison of Ah receptor-mediated luciferase and ethoxyresorufin-O-deethylase induction in H4IIE cells: implications for their use as bioanalytical tools for the detection of polyhalogenated aromatic hydrocarbons.
Toxicol. Appl. Pharmacol. 137: 316-325.
Sanderson, J.T., S.W. Kennedy, and J.P. Giesy, J. P. (1998)
In vitro induction of ethoxyresorufin O-deethylase activity and porphyrins by polyhalogenated aromatic hydrocarbons in avian primary hepatocytes.
Environ. Toxicol. Chem. 17: 2006-2018.
Sanderson, J.T., D.M. Janz, G.D. Bellward, and J.P. Giesy (1997)
Effects of embryonic and adult exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin on hepatic microsomal testosterone hydroxylase activities in great blue herons (Ardea herodias).
Environ. Toxicol. Chem. 16: 1304-1310.
Sanderson, J.T., and G.D. Bellward (1995)
Hepatic microsomal ethoxyresorufin O-deethylase-inducing potency in ovo and cytosolic Ah receptor binding affinity of 2,3,7,8-tetrachlorodibenzo-p-dioxin: comparison of four avian species.
Toxicol. Appl. Pharmacol. 132: 131-145.
Sanderson, J.T., J.E. Elliott, R.J. Norstrom, P.E. Whitehead, L.E. Hart, K.M. Cheng, and G.D. Bellward (1994)
Monitoring biological effects of polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls in great blue heron chicks (Ardea herodias) in British Columbia.
J. Toxicol. Environ. Health 41: 435-450.
Sanderson, J. T., R.J. Norstrom, J.E. Elliott, L.E. Hart, K.M. Cheng, and G.D. Bellward (1994)
Biological effects of polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls in double-crested cormorant chicks (Phalacrocorax auritus).
J. Toxicol. Environ. Health 41: 247-265.