Unscheduled DNA synthesis assay in mammalian spermatogenic cells: an update.
The unscheduled DNA synthesis (UDS) assay measures DNA repair in response to DNA damage. To date, 59 chemicals plus UV and X rays have been tested for UDS in spermatogenic cells of humans, rabbits, rats, and mice. In vivo, in vitro, and combined in vivo/in vitro procedures have been used. UDS has been shown to occur in spermatogonia, meiotic spermatocytes, and early spermatid stages. Fifty-nine percent of the agents tested gave a positive UDS response in one or more germ-cell stages. Results show 95% concordance (positive or negative) between different mammalian species. Some well-known genotoxic chemicals, for example, aflatoxin B(1) (AFB(1)), benzo[a]pyrene (B[a]P), and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), did not induce significant levels of UDS. Possible explanations are discussed. Results from the UDS assay were compared with those from the mouse specific-locus mutation (SLM) test to determine correlations between the two assays. Only two chemicals, ethyl- and methyl-nitrosourea (ENU and MNU), have been tested for UDS and SLM induction in spermatogonial stages. Results show full concordance between the two assays. In postspermatogonial stages, 25 chemicals and X rays have been tested for UDS and SLM induction. Seventy-seven percent of these agents showed similar results (positive or negative) in these germ-cell stages. Although the UDS assay cannot replace the SLM test, the strong correlations between the two assays suggest the usefulness of the UDS assay as a predictor of germ-cell mutations in mammalian systems.
Sotomayor
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Division of Toxicological Research, Center for Food Safety and Applied Nutrition, Food and Drug Administration, Laurel, Maryland 20708, USA. res@cfsan.fda.gov
Sega
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D000818:Animals; D004260:DNA Repair / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D009153:Mutagens / Q000494:pharmacology*; D009154:Mutation; D011817:Rabbits; D051381:Rats; D013094:Spermatozoa / Q000166:cytology / Q000378:metabolism*
D009153:Mutagens