Promutagenic alkyl lesions are induced in the tissue DNA of animals treated with isoniazid.
Affiliation
Paterson Institute for Cancer Research, Christie Hospital and Holt Radium Institute, Manchester, UK.Issue Date
1988-07
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Further studies have been carried out to determine mechanisms for the toxic and carcinogenic properties of isoniazid (INH) in laboratory animals. 1. Single doses of INH (1.1 mg per mouse), which if given continuously to Swiss mice result in a 50% incidence of lung tumours, lead to the formation of approximately 0.5 and approximately 0.3 mumol O6-methylguanine per mol/guanine in the DNA of liver and lung, respectively. 2. Repeated doses of INH result in a progressive decrease in the levels of O6-methylguanine in lung DNA and relatively constant levels in hepatic DNA. Treatment with equimolar doses of hydrazine result in higher levels of alkylation in the DNA of liver than of lung. 3. Comparable experiments in Wistar rats show that treatment with hydrazine is very much more effective than INH in inducing the alkylation of liver and lung DNA. 4. Immunocytochemical staining of cryostat sections of liver has been used to show that the formation of O6-methylguanine occurs mainly in the nuclei of hepatocytes. 5. These results demonstrate that treatment with INH leads to the alkylation of tissue DNA and suggest that this may arise via a hydrazine intermediate. The implications of the formation of highly promutagenic lesions in tissue DNA for INH induced toxicity and carcinogenicity are discussed.Citation
Promutagenic alkyl lesions are induced in the tissue DNA of animals treated with isoniazid. 1988, 7 (4):311-7 Hum ToxicolJournal
Human ToxicologyDOI
10.1177/096032718800700403PubMed ID
2457545Type
ArticleLanguage
enISSN
0144-5952ae974a485f413a2113503eed53cd6c53
10.1177/096032718800700403