Premium
Quantitative relationship between ethylated DNA bases and gene mutation at two loci in CHO cells
Author(s) -
Fortini P.,
Calcagnile A.,
di Muccio A.,
Bignami M.,
Dogliotti E.
Publication year - 1993
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/em.2850210209
Subject(s) - ethyl methanesulfonate , hypoxanthine guanine phosphoribosyltransferase , ethylnitrosourea , guanine , locus (genetics) , phosphoribosyltransferase , genetics , gene , microbiology and biotechnology , dna , mutation , chemistry , mutation frequency , gene mutation , hypoxanthine , biology , biochemistry , mutant , enzyme , nucleotide
In a previous study we showed that the formation of O 6 ‐ethylguanine (O 6 ‐EtGua) in the DNA of CHO cells in culture correlated with mutations induced by ethylnitrosourea (ENU) and diethylsulfate (DES) at the hypoxanthine‐guanine‐phosphoribosyltransferase ( hprt ) locus but not at the Na, K‐ATPase locus. This study was extended to another ethylating agent, ethyl methanesulfonate (EMS). DNA adduct formation and induction of mutation at the two gene loci were determined simultaneously in CHO cells after EMS exposure. The extent of ethylation at the N 7 and O 6 positions of guanine and at the N 3 site of adenine were measured and the possible correlations with 6‐thioguanine resistance (6‐TG r ) and ouabain resistance (oua r ) mutations were investigated. A good correlation between the levels of ethylation at O 6 guanine and mutation frequency at hprt gene by all three ethylating agents was observed. In the case of the oua r locus, the frequency of O 6 ‐EtGua adducts correlated with mutation induction by EMS and ENU but not by DES. Although both EMS and DES have similar reaction mechanisms, these results highlight differences in their mutational specificity. The comparison of this type of analysis with mutational spectra revealed that correlation studies may be inadequate to analyse multi‐component phenomena like mutation formation. © 1993 Wiley‐Liss, Inc.