title: Relationship between specific alkylated bases and mutations at two gene loci induced by ethylnitrosourea and diethyl sulfate in CHO cells.
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.
authors.affiliation: Laboratory of Applied Toxicology, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Bignami
authors.forename: A
authors.initials: A
authors.lastname: Vitelli
authors.forename: A
authors.initials: A
authors.lastname: Di Muccio
authors.forename: M
authors.initials: M
authors.lastname: Terlizzese
authors.forename: A
authors.initials: A
authors.lastname: Calcagnile
authors.forename: G A
authors.initials: GA
authors.lastname: Zapponi
authors.forename: P H
authors.initials: PH
authors.lastname: Lohman
authors.forename: L
authors.initials: L
authors.lastname: den Engelse
authors.forename: E
authors.initials: E
authors.lastname: Dogliotti
mesh_terms: D000477:Alkylating Agents; D000478:Alkylation; D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D006224:Cricetinae; D004249:DNA Damage; D004260:DNA Repair; D005038:Ethylnitrosourea; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D009154:Mutation; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics*; D013463:Sulfuric Acid Esters
chemical_list: D000477:Alkylating Agents; D013463:Sulfuric Acid Esters; D007041:Hypoxanthine Phosphoribosyltransferase; D000254:Sodium-Potassium-Exchanging ATPase; C011612:diethyl sulfate; D005038:Ethylnitrosourea