1-aminobenzotriazole inhibits acrylamide-induced dominant lethal effects in spermatids of male mice

Acrylamide (AA) is a germ cell mutagen and induces clastogenic effects pred ominantly in spermatids of mice. The mechanism of AA clastogenicity has bee n a matter of dispute. Since the reactivity of AA with DNA is low but is hi gh with proteins containing SH groups, it was suggested that protamine alky lation could be the mechanism of clastogenicity by AA in spermatids, This w as substantiated by the observation that the time course of protamine alkyl ation and dominant lethal effects in spermatids of mice induced by AA was s trictly parallel. Another suggestion was that AA may be metabolized by cyto chrome P-450 to the epoxide glycidamide (GA), which is then the ultimate DN A-reactive clastogen, This suggestion was based on the similarity of the st age specificity pattern for dominant lethality and heritable translocation induction by AA and GA. To test this latter assumption, 1-aminobenzotriazol e (ABT), an inhibitor of P-450 metabolism, was used in the present experime nts. Male mice were pretreated with ABT (3x50 mg/kg) on three consecutive d ays followed by AA treatment (125 mg/kg) on day 4, Parallel groups of anima ls were treated with AA (125 mg/kg), ABT (3x50 mg/kg) or with the solvent d ouble-distilled water. The experiment was repeated once with slightly varie d mating parameters. The results of both experiments showed that ABT inhibi ted or significantly reduced the AA-induced dominant lethal effects. Thus, the present data support the hypothesis that the AA metabolite GA is the ul timate clastogen in mouse spermatids.