Male-mediated dominant lethal mutations in mice following prooxidant treatment

This study's primary aim is to examine if prooxidant treatment has the propensity to induce dominant lethal (DL) type mutations in a randomly bred closed colony of CFT-Swiss mice. Initially, graded doses of both organic hydroperoxides viz., t-butyl hydroperoxide (tbHP), and cumene hydroperoxide (cHP) were administered (i.p.) to adult males and the mortality data was analysed to determine the LD50 values. cHP was relatively more toxic compared to tbHP. The computed LD50 values were 1500 and 3000 mu mol (kg body weight)(-1) for cHP and tbHP, respectively. Subsequently, adult males were administered (i.p.) with 1/10 LD50 doses of hydroperoxide (HP) (tbHP - 30 mu mol (100 g body weight)(-1) and cHP - 15 mu mol (100 g body weight)(-1)) on 5 consecutive days and were mated with virgin females for a period of 5 weeks to characterise the male-mediated DL mutations. Male-based analysis of the three major variables viz., implantations, live embryos and dead implants (DI) were carried out to assess the DL-type response induction. While tbHP induced significant increases (2- to 5-fold) in the incidence of DI during the first 4 weeks, cHP induced a marginal increase only during the first week. These results suggest that prooxidants induce DL-type effect only in specific post-meiotic stages of spermatogenesis and stress the need to further investigate the implications of chronic oxidative stress on the male reproductive system. (C) 1999 Elsevier Science B.V. All rights reserved.