Abstract:
:The genotoxicity of alpha-hexachlorocyclohexane (alpha-HCH) was evaluated in primary cultures of mouse, rat and human hepatocytes. DNA fragmentation was measured by the alkaline elution technique and DNA repair synthesis by quantitative autoradiography. A 20 h exposure to subtoxic concentrations ranging from 0.056 to 0.32 mM produced a dose-dependent frequency of DNA breaks in rat hepatocytes and in hepatocytes from four of five human donors, but not in mouse hepatocytes, DNA repair induction was absent in hepatocytes from all three species. The reduction in the frequency of DNA breaks observed in rat hepatocytes simultaneously exposed to metyrapone suggests that alpha-HCH is transformed into reactive species by a cytochrome P450-dependent reaction. The detection of DNA fragmentation but not of DNA repair synthesis may be tentatively explained by assuming that alpha-HCH behaves as a chemical eliciting short patch DNA repair, which is more easily revealed as genotoxic by the occurrence of DNA single-strand breaks.
journal_name
Mutagenesisjournal_title
Mutagenesisauthors
Mattioli F,Robbiano L,Adamo D,Federa R,Martelli A,Brambilla Gdoi
10.1093/mutage/11.1.79subject
Has Abstractpub_date
1996-01-01 00:00:00pages
79-83issue
1eissn
0267-8357issn
1464-3804journal_volume
11pub_type
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