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 microM, human and rat), benomyl (10 to 100 microM, human and rat), thiotepa (10 to 1000 microM, human and rat), cisplatin (30 to 1000 microM, human; 100 to 1000 microM, rat), Cd2+ (30 to 1000 microM, human; 100 to 1000 microM, rat), and acrylonitrile (30 to 1000 microM, human; 30 to 300 microM, rat). Four chemicals induced significant levels of ssDNA breaks in testicular cells from both species: styrene oxide (> or = 100 microM, rat and human), 1,2-dibromoethane (EDB) (> or = 100 microM, rat; 1000 microM human), thiram (> or = 30 microM, rat; > or = 100 microM, human), and chlordecone (300 microM, rat; > or = 300 microM, 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) (> or = 10 microM), 1,3-dinitrobenzene (1,3-DNB) (> or = 300 microM), Cr6+ (1000 microM), and aflatoxin B1 (> or = 100 microM), 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 microM, 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.
Bjørge
C
C
Department of Environmental Medicine, National Institute of Public Health, Oslo, Norway.
Brunborg
G
G
Wiger
R
R
Holme
J A
JA
Scholz
T
T
Dybing
E
E
Søderlund
E J
EJ
D000328:Adult; D000368:Aged; D000818:Animals; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005854:Germ Cells / Q000187:drug effects*; D006801:Humans; D007306:Insecticides / Q000633:toxicity; D008297:Male; D008875:Middle Aged; D009153:Mutagens / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013737:Testis / Q000166:cytology / Q000187:drug effects*
D007306:Insecticides; D009153:Mutagens; D004247:DNA