Relationship between specific alkylated bases and mutations at two gene loci induced by ethylnitrosourea and diethyl sulfate in CHO cells

Mutat Res. 1988 Jan;193(1):43-51. doi: 10.1016/0167-8817(88)90006-5.

Abstract

DNA adduct formation and induction of mutations at 2 gene loci, hypoxanthine-guanine-phosphoribosyltransferase (HPRT) and Na,K-ATPase, were determined simultaneously in Chinese hamster ovary (CHO) cells after treatment with 2 ethylating agents, ethylnitrosourea (ENU) or diethyl sulfate (DES). Doses of DES and ENU, which resulted in equal levels of O6-ethylguanine (O6-EtGua) and O4-ethylthymine (O4-EtThy) in the DNA, were found to induce very similar frequencies of 6-thioguanine-resistant (6-TGr) mutants. Formation of these DNA adducts might therefore be correlated with mutations induced at the HPRT locus. When, however, the same analysis was applied to ouabain-resistant (ouar) mutants, it was found that, at similar levels of O6-EtGua and O4-EtThy, DES induced many more ouar mutants than ENU. This result supports the notion that primary DNA lesions other than O6-EtGua and O4-EtThy are involved in the fixation of ENU- and DES-induced mutations at the Na,K-ATPase gene locus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylating Agents*
  • Alkylation
  • Animals
  • Cell Line
  • Cell Survival
  • Cricetinae
  • DNA Damage*
  • DNA Repair
  • Ethylnitrosourea
  • Hypoxanthine Phosphoribosyltransferase / genetics*
  • Mutation*
  • Sodium-Potassium-Exchanging ATPase / genetics*
  • Sulfuric Acid Esters

Substances

  • Alkylating Agents
  • Sulfuric Acid Esters
  • Hypoxanthine Phosphoribosyltransferase
  • Sodium-Potassium-Exchanging ATPase
  • diethyl sulfate
  • Ethylnitrosourea