Sensitization and co-exposure synergy of testicular toxicant exposure

ENVR 97

Jeffrey S. Moffit, jeffrey_moffit@brown.edu, Bronwyn H. Bryant, bronwyn_bryant@brown.edu, Susan J. Hall, susan_hall@brown.edu, and Kim Boekelheide, kim_boekelheide@brown.edu. Department of Pathology and Laboratory Medicine, Brown University, Box G-E5, Providence, RI 02912
Determining the health risks of complex mixtures from single chemical exposures can be precarious given antagonistic, additive or synergistic interactions between chemicals. Testicular toxicants disrupt spermatogenesis by targeting Leydig, Sertoli and germ cell populations and by activating or inhibiting numerous molecular pathways. Given the complexity of the cellular targets and exposures, little mechanistic data are available concerning the effects of co-exposures to testicular toxicants. The environmental pollutants, 2,5 hexanedione (2,5-HD) and carbendazim (CBZ) are presumed to elicit Sertoli cell dysfunction and testicular toxicity by disrupting microtubule polymerization. Despite their antagonistic mechanisms of action on tubulin assembly, 2,5-HD and CBZ co-exposure synergistically disrupt spermatogenesis in rats. Further study is underway to evaluate the response of a second testicular toxicant to a 2,5-HD priming exposure. Ultimately, gene expression analysis from these co-exposures will be utilized to understand how molecular alterations of the seminiferous epithelium and co-exposures predispose the testis to toxicant-induced injury.
 

Environmental Contaminants: Low-Level and Complex Mixtures
1:30 PM-4:50 PM, Wednesday, August 22, 2007 Boston Park Plaza -- Stanbro Rm, Oral

Division of Environmental Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007