Relationship between specific alkylated bases and mutations at two gene loci induced by ethylnitrosourea and diethyl sulfate in CHO cells.
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.
Bignami
M
M
Laboratory of Applied Toxicology, Istituto Superiore di Sanità, Rome, Italy.
Vitelli
A
A
Di Muccio
A
A
Terlizzese
M
M
Calcagnile
A
A
Zapponi
G A
GA
Lohman
P H
PH
den Engelse
L
L
Dogliotti
E
E
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
D000477:Alkylating Agents; D013463:Sulfuric Acid Esters; D007041:Hypoxanthine Phosphoribosyltransferase; D000254:Sodium-Potassium-Exchanging ATPase; C011612:diethyl sulfate; D005038:Ethylnitrosourea