Stability and capacity of dimethylnitrosamine-induced 06-methylguanine repair system in rat liver

Ruggero Montesano, Henriette Brésil, Ghyslaine Planche-Martel, Ghyslaine Planche-Martel, Anthony E. Pegg

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Abstract

Repeated administration of dimethylnitrosamine (DMN) (2 mg/kg for 3 weeks) to BD IV rats results in an increased capacity for the liver to repair O6-methylguanine in DNA, whereas other DNA adducts (7-methylguanine and 3-methyladenine) are not affected. In the experiments reported here, data on the rapidity of action of the enhanced system, its capacity after different challenging doses of [14C]DMN (0.2, 2.0, and 20 mg/kg), and the persistence after cessation of the DMN pretreatment are described. The results show that, after a dose of [14C]DMN (2.0 mg/kg), the increased activity acts very rapidly (10 min) repairing O6-methylguanine as soon as it is formed and that, by 2 hr, 65% of the O6-methyiguanine generated in liver DNA has already been removed. Very little removal of O6-methylguanine occurs within this time in control rats not receiving any DMN pretreatment. The DMN-induced repair activity is of limited capacity, since its effect can be detected after DNA damage induced by 0.2 or 2.0 mg of [14C]DMN per kg, whereas this activity has little impact on the O6-methylguanine generated in liver DNA by 20 mg of [14C]DMN per kg. Upon cessation of the DMN pretreatment, the enhanced repair activity, as determined also by the in vitro activity of the O8-methyltransferase, decays slowly, but after 25 days, the repair activity is still higher than control values. No correlation was observed between increased [3H]thymidine incorporation in liver DNA and increased O6-methylguanine repair, indicating that liver cell proliferation is not necessarily coupled with an elevated methyltransferase level. Research.

Original languageEnglish (US)
Pages (from-to)5808-5814
Number of pages7
JournalCancer Research
Volume43
StatePublished - Dec 1 1983

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Montesano, R., Brésil, H., Planche-Martel, G., Planche-Martel, G., & Pegg, A. E. (1983). Stability and capacity of dimethylnitrosamine-induced 06-methylguanine repair system in rat liver. Cancer Research, 43, 5808-5814.