A comparative study of chemically induced DNA damage in isolated human and rat testicular cells

Testicular cells prepared from human organ transplant donors or from Wistar rats were used to compare 15 known reproductive toxicants with respect to their ability to induce DNA damage, measured as single-strand DNA breaks and alkali labile sites (ssDNA breaks) with alkaline filter elution. The compounds tested included various categories of chemicals (i.e., pesticides, industrial chemicals, cytostatics, and mycotoxins) most of which are directly acting genotoxicants (i.e., reacting with DNA either spontaneously or via metabolic activation). In addition, a few indirect genotoxic and nongenotoxic reproductive toxicants were included. Six of the chemicals induced no significant levels of ssDNA breaks in human and rat testicular cells: methoxychlor (10 to 100 mu M, human and rat), benomyl (10 to 100 mu M, human and rat), thiotepa (10 to 1000 mu M, human and rat), cisplatin (30 to 1000 mu M, human; 100 to 1000 mu M, rat), Cd2+ (30 to 1000 mu M, human; 100 to 1000 mu M, rat), and acrylonitrile (30 to 1000 mu M, human; 30 to 300 mu M, rat). Four chemicals induced significant levels of ssDNA breaks in testicular cells from both species: styrene oxide (greater than or equal to 100 mu M, rat and human), 1,2-dibromoethane (EDB) (greater than or equal to 100 mu M, rat; 1000 mu M human), thiram (greater than or equal to 30 mu M, rat; greater than or equal to 100 mu M, human), and chlordecone (300 mu M, rat; greater than or equal to 300 mu M, human). Finally, five chemicals induced ssDNA breaks in one of the two species. Four chemicals induced significant ssDNA breaks in rat testicular cells only: 1,2-dibromo-3-chloropropane (DBCP) (greater than or equal to 10 mu M), 1,3-dinitrobenzene (1,3-DNB) (greater than or equal to 300 mu M), Cr6+ (1000 mu M), and aflatoxin B-1 (greater than or equal to 100 mu M), the last two of these produced only a minor positive response. One chemical, acrylamide, induced a marginal increase in ssDNA breaks in human at 1000 mu M, but not in rat testicular cells. Although based on a limited number of donors, the data indicate a close correlation between the induction of DNA damage in human and rat testicular cells in vitro. For some chemicals, however, there appears to be differences in the susceptibility to chemically induced ssDNA breaks of isolated testicular cells from the two species. The data indicate that the parallel use of human and rat testicular cells provides a valuable tool in the assessment of human testicular toxicity. (C) 1996 Elsevier Science Inc.