Methylation of liver DNA guanine in hamsters given hydrazine
| Autor: | William S. Bosan, Ronald C. Shank |
|---|---|
| Rok vydání: | 1983 |
| Předmět: |
Male
medicine.medical_specialty S-Adenosylmethionine Guanine Time Factors Hamster Toxicology Methylation chemistry.chemical_compound Internal medicine Cricetinae medicine Monomethylhydrazine Animals Buthionine sulfoximine Hydrazine (antidepressant) Pharmacology biology Dose-Response Relationship Drug Mesocricetus Chemistry DNA biology.organism_classification Glutathione Endocrinology Hydrazines Biochemistry Liver DNA methylation Hydrazine sulfate |
| Zdroj: | Toxicology and applied pharmacology. 70(2) |
| ISSN: | 0041-008X |
| Popis: | Formation of 7-methylguanine and O6-methylguanine in liver DNA was measured 24 hr after administration of various single oral doses of 15 to 120 mg hydrazine/kg body wt to Syrian golden hamsters, and at various times up to 96 hr after a single oral dose of 90 mg hydrazine/kg body wt. Formation of these bases in hamster liver DNA appeared similar to that reported earlier for rats and mice treated with necrogenic doses of hydrazine; however, persistence of O6-methylguanine in liver DNA following hydrazine administration was longer in hamster than in rat liver DNA. Administration of hydrazine sulfate in the drinking water of hamsters over a 9-week period resulted in accumulation of both 7-methylguanine and O6-methylguanine in liver DNA to the extent that about 2 out of every 10,000 guanine bases were methylated at each position on the base. Diethyl maleate pretreatment of hamsters depleted liver stores of glutathione and blocked DNA methylation in hydrazine-treated animals; however, buthionine sulfoximine, which also depleted glutathione stores, had no effect on the DNA methylation response to hydrazine poisoning in Sprague-Dawley rats. Hydrazine administration to hamsters and Swiss Webster mice resulted in more 7-methylguanine and O6-methylguanine in liver DNA than did administration of monomethylhydrazine, a proposed intermediate in the hydrazine-DNA methylation response. Even at the highest feasible dose of monomethylhydrazine to hamsters, no methylguanines could be detected, while these aberrant bases were readily quantifiable following hydrazine administration; thus, no evidence was obtained to support the proposal that monomethylhydrazine is an important intermediate in the methylation of DNA guanine in hydrazine-treated animals. |
| Databáze: | OpenAIRE |
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