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Cited by 43Carcinogens and Genotoxicity AssessmentSperm and Testicular FunctionEffects of Radiation Exposure

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

Doreswamy, K., Muralidhara·2005·Toxicology
DOI 10.1016/j.tox.2004.07.010
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Abstract

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.

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Metadata

Authors
Doreswamy, K., & Muralidhara
Affiliations
Central Food Technological Research Institute (IN)
ORCID
Doreswamy, K.
Venue
Toxicology
Publisher
Elsevier BV
Published
2005-01
Volume
206
Issue
1
Pages
169-178
ISSN
0300-483X (ISSN-L)
DOI
10.1016/j.tox.2004.07.010
OpenAlex
W2165157310
Cited by
43
References
2
Citations by year
2025: 3 · 2024: 1 · 2023: 2 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 4 · 2017: 2 · 2016: 2 · 2015: 4 · 2014: 2 · 2013: 1 · 2012: 2
FWCI
0.83
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Toxicology (publishedVersion)
  • PubMed (publishedVersion)
  • CFTRI Institutional Repository (acceptedVersion)
Funders
Department of Science and Technology, Ministry of Science and Technology, India
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
  • Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
Keywords
iron dextran, testis, oxidative stress, lipid peroxidation, DNA damage, spermatogenesis, sperm abnormalities, dominant lethal mutations, protein carbonyls, antioxidant enzymes, genotoxicity, iron overload, postmeiotic germ cells
MeSH terms
Animals, Catalase, DNA Damage, Female, Fertility, Genes, Dominant, Genes, Lethal, Glutathione, Glutathione Peroxidase, Iron-Dextran Complex, Lipid Peroxides, Liver, Male, Mutagens, Mutation, Organ Size, Pregnancy, Sperm Head, Superoxide Dismutase, Testis, Oxidative Stress, Embryo Loss, Mice

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