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Genotoxic consequences associated with oxidative damage in testis of mice subjected to iron intoxication

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Relation http://ir.cftri.com/1497/
T_03_05
 
Title Genotoxic consequences associated with oxidative damage in testis of mice subjected to iron intoxication
 
Creator Doreswamy, K.
Muralidhara, Dr.
 
Subject 09 Human Physiology
17 Toxicology
 
Description While iron-induced testicular dysfunction has been demonstrated adequately, the mechanism(s) involved and the genotoxic implications are not fully understood. In order to understand the genotoxic effects of iron intoxication, initially induction of oxidative stress response in testis of adult albino mice (CFT-Swiss) was ascertained following administration (i.p.) of acute sub-lethal doses of iron dextran (ID). Subsequently, multiple sub-lethal doses (50, 100 and 200 mg/kg bw/day) were employed to characterize effects on lipid peroxidation (LPO) in testis (homogenates, microsomal/mitochondrial fractions), DNA damage and incidence of abnormal sperms. While acute doses of ID induced only a marginal increase in LPO response in testis at 24 h of administration, multiple doses elicited a moderate (30–40%) increase in LPO in whole homogenates and significant dose-related elevation in both mitochondrial (20–45%) and microsomal fractions (25–65%). This was associated with significant increase in
DNA damage in the testis as evidenced by increased single strand breaks in a fluorimetric analysis of DNA unwinding (FADU) assay. Further, evidences of oxidative damage in testis was evident in terms of increased protein carbonyls and altered antioxidant enzymic activities. The genotoxic implications were investigated by quantification of the frequency of abnormal sperms sampled at specific periods during spermatogenetic cycle. Nearly three- to seven-fold increase in percent abnormal sperms among the ID
treated males were evident during the first 3 weeks although the counts were unaffected. Interestingly, in a classical dominant lethal (DL) assay, mating of ID treated (100 mg/kg bw/day for 5 days) males sequentially for a period of 5 weeks with untreated females resulted in a significant increase in male-mediated dominant lethal type mutations (the frequency of dead implants)
during the first 3 weeks only indicating a stage-specific effect on post-meiotic germ cells. These findings provide an account of the early oxidative damage in testis in vivo following exposure to low levels of iron which may be wholly or in part responsible for the genotoxic consequences observed in this model of iron overload.
 
Date 2005
 
Type Article
PeerReviewed
 
Format application/pdf
 
Language en
 
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Identifier http://ir.cftri.com/1497/1/Toxicology_206_%282005%29_169-178.pdf
Doreswamy, K. and Muralidhara, Dr. (2005) Genotoxic consequences associated with oxidative damage in testis of mice subjected to iron intoxication. Toxicology, 206. pp. 169-178.