Low-level exposure to environmental pollutants such as BDO 2 contributes directly and indirectly to an increase in PCa. The aim of this study was to define the cellular changes associated with micro-doses of Butadiene Diepoxide (BDO 2 ) in prostate cancer cells. We observed that micro-doses of BDO 2 resulted in dose- and time-dependent increases in cytotoxicity and increased expression of prostate tumor markers in LNCaP(AR + ) and DU145(AR - ) cells. There was an increased sensitivity of DU145(AR - ) cells to BDO 2 toxicity which was reversed by transient transfection of AR into theses cell. Exposure of prostate cells to BDO 2 increases cytotoxicity, and apoptosis, which correlates with increases in caspases and Bcl2 protein and mRNA levels. In cell DU145(AR - ) cell transient transfected with a functional AR, the levels of cytotoxicity and caspase activity were decreased in the presence of BDO 2 , but BDO 2 -induced apoptotic protein expression was unaltered. This study provides evidence that micro-doses of BDO 2 modulate prostate cell toxicity by promoting apoptosis and tumor gene expression .
D. Anderson, “Butadiene: Species Comparison for Metabolism and Genetic Toxicology,” Mutation Research, Vol. 405, No. 2, 1998, pp. 247-258. doi:10.1016/S0027-5107(98)00142-0
D. Anderson, “Genetic and Reproductive Toxicity of Butadiene and Isoprene,” Chemico-Biological Interactions, Vol. 135-136, 2001, pp. 65-80. doi:10.1016/S0009-2797(01)00171-5
M. Christian, “Review of Reproductive and Developmental Toxicity of 1,3-Butadiene,” Toxicology, Vol. 113, No. 1-3, 1996, pp. 137-143. doi:10.1016/0300-483X(96)03438-5
E. Delzell, N. Sathiakumar, J. Graff, M. Macaluso, G. Maldonado and R. Matthews, “An Updated Study of Mortality among North American Synthetic Rubber Industry Workers,” Research Report (Health Effects Institute), Vol. 132, 2006, pp. 1-63, 65-74.
E. Delzell, N. Sathiakumar, M. Hovinga, M. Macaluso, J. Julian, R. Larson, P. Cole and D. Muir, “A Follow-Up Study of Synthetic Rubber Workers,” Toxicology, Vol. 113, No. 1-3, 1996, pp. 182-189. doi:10.1016/0300-483X(96)03443-9
M. Goggin, J. A. Swenberg, V. E. Walker and N. Tretyakova, “Molecular Dosimetry of 1,2,3,4-Diepoxybutane-induced DNA-DNA Cross-Links in B6C3F1 Mice and F344 Rats Exposed to 1,3-Butadiene by Inhalation,” Cancer Research, Vol. 69, 2009, pp. 2479-2486. doi:10.1158/0008-5472.CAN-08-4152
D. Anderson, “Male-Mediated Developmental Toxicity,” Toxicology and Applied Pharmacology, Vol. 207, No. 2, 2005, pp. 506-513. doi:10.1016/j.taap.2005.01.022
P. Boffetta, H. O. Adami, P. Cole, D. Trichopoulos and J. S. Mandel, “Epidemiologic Studies of Styrene and Cancer: A Review of the Literature,” Journal of Occupational & Environmental Medicine, Vol. 51, No. 11, 2009, pp. 1275-1287. doi:10.1097/JOM.0b013e3181ad49b2
H. Ma, T. G. Wood, M. M. Ammenheuser, J. I. Rosenblatt and J. B. Ward Jr., “Molecular Analysis of hprt Mutant Lymphocytes from 1,3-Butadiene-exposed Workers,” Environmental and Molecular Mutagenesis, Vol. 36, 2000, pp. 59-71.
F. Pacchierotti, C. Tiveron, R. Ranaldi, B. Bassani, E. Cordelli, G. Leter and M. Spanò, “Reproductive Toxicity of 1,3-Butadiene in the Mouse: Cytogenetic Analysis of Chromosome Aberrations in First-Cleavage Embryos and Flow Cytometric Evaluation of Spermatogonial Cell Killing,” Mutational Research, Vol. 397, No. 1, 1998, pp. 55-66.
J. Huff, R. Melnick, H. Solleveld, J. Haseman, M. Powers, and R. Miller, “Multiple Organ Carcinogenicity of 1,3-Butadiene in B6C3F Mice after 60 Weeks of Inhalation Exposure,” Science, Vol. 227, No. 4686, 1985, pp. 548-549. doi:10.1126/science.3966163
M. Macaluso, R. Larson, E. Delzell, N. Sathiakumar, M. Hovinga, J. Julian, D. Muir and P. Cole, “Leukemia and Cumulative Exposure to Butadiene, Styrene and Benzene among Workers in the Synthetic Rubber Industry,” Toxicology, Vol. 113, No. 1-3, 1996, pp. 190-202. doi:10.1016/0300-483X(96)03444-0
E. Mylchreest, L. A. Malley, A. J. O’Neill, T. A. Kegelman, G. P. Sykes and R. Valentine, “Reproductive and Developmental Toxicity of Inhaled 2,3-Dichloro-1,3-butadiene in Rats,” Reproductive Toxicology, Vol. 22, No. 4, 2006, pp. 613-622. doi:10.1016/j.reprotox.2006.04.002
M. Schmiederer, E. Knutson, P. Muganda and T. Albrecht, “Acute Exposure of Human Lung Cells to 1,3-Butadiene Diepoxide Results in G1 and G2 Cell Cycle Arrest,” Environmental and Molecular Mutagenesis, Vol. 45, No. 4, 2005, pp. 354-364. doi:10.1002/em.20099
S. Naragoni, S. Sankella, K. Harris and W. G. Gray, “Phytoestrogens Regulate mRNA and Protein Levels of Guanine Nucleotide-Binding Protein, Beta-1 Subunit (GNB1) in MCF-7 Cells,” Journal of Cellular Physiology, Vol. 219, No. 3, 2009, pp. 584-594. doi:10.1002/jcp.21699
R. Solipuram, S. Koppula, A. Hurst, K. Harris, S. Naragoni, K. Fontenot and W. Gray, “Molecular and Biochemical Effects of Kola Nut Extract on Androgen Receptor-Mediated Pathways,” Journal of Toxicology, Vol. 2009, 2009, Article ID: 530279. doi:10.1155/2009/530279
A. Biosystem, “User Bulletin #2: ABI PRISM 7700 Sequence Detection System,” 2001.
S. Stahl, T. Y. Chun and W. G. Gray, “Phytoestrogens Act as Estrogen Agonists in an Estrogen-Responsive Pituitary Cell Line,” Toxicology and Applied Pharmacology, Vol. 152, No. 1, 1998, pp. 41-48. doi:10.1006/taap.1998.8500
W. Washington, L. Hubert, D. Jones and W. G. Gray, “Bisphenol a Binds to the Low-Affinity Estrogen Binding Site,” In Vitro & Molecular Toxicology, Vol. 14, No. 1, 2001, pp. 43-51. doi:10.1089/109793301316882531
P. I. GraphPad, “GraphPad,” 5th Edition, GraphPad Software, Inc., San Diego, 1997.
C. Lee, D. M. Sutkowski, J. A. Sensibar, D. Zelner, I. Kim, I. Amsel, N. Shaw, G. S. Prins and J. M. Kozlowski, “Regulation of Proliferation and Production of Prostate-Specific Antigen in Androgen-Sensitive Prostatic Cancer Cells, LNCaP, by Dihydrotestosterone,” Endocrinology, Vol. 136, No. 2, 1995, pp. 796-803. doi:10.1210/en.136.2.796
T. V. Nguyen, M. Yao and C. J. Pike, Flutamide and Cyproterone Acetate Exert Agonist Effects: Induction of Androgen Receptor-Dependent Neuroprotection,” Endocrinology, Vol. 148, No. 6, 2007, pp. 2936-2943. doi:10.1210/en.2006-1469
X. B. Liao, S. Q. Tang, T. J. Brantley, L. G. Tomas and B. Y. Li, “Small-Interfering RNA-Induced Androgen Receptor Silencing Leads to Apoptotic Cell Death in Prostate Cancer,” Molecular Cancer Therapeutics, Vol. 4, 2005, pp. 505-515. doi:10.1158/1535-7163.MCT-04-0313
P. Thelen, P. Burfeind, S. Schweyer, J. G. Scharf, W. Wuttke and R. H. Ringert, “Molecular Principles of Alternative Treatment Approaches for Hormone-Refractory Prostate Cancer,” Der Urologe, Vol. 46, No. 9, 2007, pp. 1271-1274. doi:10.1007/s00120-007-1452-0
P. Thelen, T. Peter, A. Hunermund, S. Kaulfuss, D. Seidlova-Wuttke, W. Wuttke, R. H. Ringert and F. Seseke, “Phytoestrogens from Belamcanda Chinensis Regulate the Expression of Steroid Receptors and Related Cofactors in LNCaP Prostate Cancer Cells,” BJU International, Vol. 100, No. 1, 2007, pp. 199-203. doi:10.1111/j.1464-410X.2007.06924.x
W.-M. B. Thomas, Z. Liao, S. Kim, S. Lemeshow, J. W. Erdman and S. K. Clinton, “Prostate Carcinogenesis in N-Methyl-N-nitrosourea (NMU)-Testosterone-Treated Rats Fed Tomato Powder, Lycopene, or Energy-Restricted Diets,” Journal of the National Cancer Institute, Vol. 95, No. 21, 2003, pp. 1578-1586. doi:10.1093/jnci/djg081
P. Wang, Q. Ma, J. Luo, B. Liu, F. Tan, Z. Zhang and Z. Chen, “Nkx3.1 and p27(KIP1) Cooperate in Proliferation Inhibition and Apoptosis Induction in Human Androgen-Independent Prostate Cancer Cells,” Cancer Investigation, Vol. 27, No. 4, 2009, pp. 369-375. doi:10.1080/07357900802232749
H. G. Yoon and J. Wong, “The Corepressors Silencing Mediator of Retinoid and Thyroid Hormone Receptor and Nuclear Receptor Corepressor Are Involved in Agonist- and Antagonist-Regulated Transcription by Androgen Receptor,” Molecular Endocrinology, Vol. 20, No. 5, 2006, pp. 1048-1060. doi:10.1210/me.2005-0324
L. Yu, G. L. Blackburn and J. R. Zhou, “Genistein and Daidzein Downregulate Prostate Androgen-Regulated Transcript-1 (PART-1) Gene Expression Induced by Dihydrotestosterone in Human Prostate LNCaP Cancer Cells,” The Journal of nutrition, Vol. 133, No. 2, 2003, pp. 389-392.
R. Kavlok and A. Cummings, “Androgen Receptor Function—Vinclozolin-Induced Malformations in Reproductive Development,” Critical Reviews in Toxicology, Vol. 35, 2005, pp. 721-726. doi:10.1080/10408440591007377
P. J. Mink, H.-O. Adami, D. Trichopoulos, N. L. Britton and J. S. Mandel, “Pesticides and Prostate Cancer: A Review of Epidemiologic Studies with Specific Agricultural Exposure Information,” European Journal of Cancer Prevention, Vol. 17, No. 2, 2008, pp. 97-110. doi:10.1097/CEJ.0b013e3280145b4c
G. S. Prins, “Endocrine Disruptors and Prostate Cancer Risk,” Endocrine-Related Cancer, Vol. 15, 2008, pp. 649-656. doi:10.1677/ERC-08-0043
L. A. Plaskon, D. F. Penson, T. L. Vaughan and J. L. Stanford, “Cigarette Smoking and Risk of Prostate Cancer in Middle-Aged Men,” Cancer Epidemiology, Biomarkers & Prevention, Vol. 12, 2003, pp. 604-609.