Exposure of HeLa cells to 0(6)-alkylguanines increases sensitivity to the cytotoxic effects of alkylating agents

Biochem Biophys Res Commun. 1985 Oct 15;132(1):178-85. doi: 10.1016/0006-291x(85)91004-6.

Abstract

Exposure of HeLa S3 cells to 0.4mM 0(6)-methylguanine or 0(6)-n-butylguanine for 24 h led to a substantial decrease in the activity of 0(6)-alkylguanine-DNA alkyltransferase. Such pretreatment caused a marked increase in the sensitivity of the cells to the cytotoxic effects of the cross-linking alkylating agent 1-(2-chloroethyl)-1-nitroso-3-cyclohexylurea and a smaller increase in the sensitivity to N-methyl-N'-nitro-N-nitrosoguanidine. These results indicate that the repair of DNA by the alkyltransferase plays an important role in the protection of cells from the cytotoxic effects of certain alkylating agents particularly those such as 1-(2-chloroethyl)-1-nitroso-3-cyclohexylurea which ultimately lead to the formation of lethal interstrand cross-links.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Division
  • DNA Repair
  • Guanine / analogs & derivatives*
  • Guanine / pharmacology
  • HeLa Cells / drug effects*
  • Humans
  • Lomustine / pharmacology
  • Methylnitronitrosoguanidine / pharmacology
  • Methyltransferases / metabolism
  • O(6)-Methylguanine-DNA Methyltransferase
  • Time Factors

Substances

  • Methylnitronitrosoguanidine
  • Guanine
  • O(6)-n-butylguanine
  • Lomustine
  • O-(6)-methylguanine
  • Methyltransferases
  • O(6)-Methylguanine-DNA Methyltransferase