Effect of pretreatment with other dialkylnitrosamines on excision from hepatic DNA of O6-methylguanine produced by dimethylnitrosamine

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Pretreatment with diethylnitrosamine or dipropylnitrosamine increased the amount of labelled O6-methylguanine found in liver DNA 4 and 24 h after injection of 10 μg/kg [3H] dimethylnitrosamine. Dibutylnitrosamine treatment had a similar, though smaller effect at 4 h but was ineffective when measurements were made 24 h after the dimethylnitrosamine was given. These pretreatments did not affect 7-methylguanine levels in the DNA showing that the metabolic conversion of dimethylnitrosamine into a methylating agent was not altered. Previous studies have shown that O6-methylguanine is rapidly removed from hepatic DNA after methylation to a small extent but removal is less efficient after higher amounts of methylation. Therefore, the most probable explanation for the present findings is that these longer dialkylnitrosamines produce a similar product in DNA which interferes with the loss of O6-methylguanine. This hypothesis was supported by experiments showing that diethylnitrosamine did give rise to O6-ethylguanine which was lost from the DNA at a rate comparable to the observed loss of O6-methylguanine in diethylnitrosamine pretreated rats. This method may, therefore, be of value for determination of whether other nitrosamines, not available in a radioactively labelled form, react with DNA at external oxygen atoms. The present results also suggest that different dialkylnitrosamines might have additive effects in prolonging damage to DNA which could be important in carcinogenesis.

Original languageEnglish (US)
Pages (from-to)109-116
Number of pages8
JournalChemico-Biological Interactions
Issue number1
StatePublished - Jan 1 1978

All Science Journal Classification (ASJC) codes

  • Toxicology

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