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Male-mediated dominant lethal mutations in mice following prooxidant treatment
1Department of Biochemistry and Nutrition, Central Food Technological Research Institute, Mysore, India.
Abstract:
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 LD(50) values. cHP was relatively more toxic compared to tbHP. The computed LD(50) values were 1500 and 3000 micromol (kg body weight)(-1) for cHP and tbHP, respectively. Subsequently, adult males were administered (i.p.) with 1/10 LD(50) doses of hydroperoxide (HP) (tbHP--30 micromol (100 g body weight)(-1) and cHP - 15 micromol (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.
Insights
Prooxidant hydroperoxides induced dominant lethal mutations in male mice, particularly t-butyl hydroperoxide, suggesting oxidative stress impacts male reproductive health.
Area of Science:
- Toxicology
- Reproductive Biology
- Genetics
Background:
- Oxidative stress is implicated in various health issues.
- The impact of prooxidants on male reproductive mutations requires further investigation.
Purpose of the Study:
- To investigate the potential of prooxidant treatment to induce dominant lethal (DL) mutations in male mice.
- To assess the dose-dependent toxicity and mutagenic effects of organic hydroperoxides.
Main Methods:
- Administered graded doses of t-butyl hydroperoxide (tbHP) and cumene hydroperoxide (cHP) to adult male mice to determine LD(50) values.
- Treated male mice with 1/10 LD(50) doses of hydroperoxides for 5 consecutive days and mated them with virgin females.
- Analyzed implantations, live embryos, and dead implants (DI) to assess DL-type mutations.
Main Results:
- Cumene hydroperoxide (cHP) was more toxic than t-butyl hydroperoxide (tbHP).
- tbHP significantly increased dead implants (DI) in the first 4 weeks of mating.
- cHP showed a marginal increase in DI only in the first week.
Conclusions:
- Prooxidant treatment can induce dominant lethal-type effects, specifically impacting post-meiotic stages of spermatogenesis.
- Chronic oxidative stress may have significant implications for male reproductive health.