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Mutational specificities of environmental carcinogens in the lacl gene of Escherichia coli H. V: DNA sequence analysis of mutations in bacteria recovered from the liver of swiss mice exposed to 1,2‐dimethylhydrazine, azoxymethane, and methylazoxymethanolacetate
Author(s) -
Zeilmaker Marco J.,
Horsfall Michael J.,
van Helten José B. M.,
Glickman Barry W.,
Mohn Georges R.
Publication year - 1991
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.2940040304
Subject(s) - biology , azoxymethane , frameshift mutation , microbiology and biotechnology , guanine , cytosine , gene , genetics , mutation , mutagenesis , escherichia coli , gene mutation , transition (genetics) , coding region , carcinogen , dna , mutation frequency , carcinogenesis , nucleotide
The host‐mediated assay (HMA) was used to determine the spectra of mutations induced in the lacl gene of Escherichia coli cells recovered from the livers of Swiss mice exposed to the carcinogens 1,2‐dimethylhydrazine (SDMH), azoxymethane (AOM), and methylazoxymethanolacetate (MAMA). These spectra were further compared with changes induced by dimethylnitrosamine (DMNA) in the HMA methodology. A total of 177 independent lacl mutations arising in the HMA following exposure to SDMH, AOM, and MAMA were analyzed. Single‐base substitutions accounted for 97% of all mutations analyzed. The vast majority of the single‐base substitutions consisted of G:C→ A:T transitions (94% of all mutations). The remaining mutations consisted of A:T →G:C transitions (3% of all mutations) while non‐base substitutions accounted for only 3% of the total mutagenesis. The latter mutations consisted of one frameshift mutation and four lacO deletions. The distribution of G:C→ A:T transitions induced by the three chemicals in the first 200 bp of the lacO gene was not random, but rather clustered at sites where a target guanine was flanked at the 5′ site by a purine residue.