Concurrent detection of gene mutations and chromosomal aberrations induced in vivo in somatic cells

Abstract

A simple direct assay for gene mutations in vivo is the missing assay in genetic toxicology. Here we report that both gene mutations and chromosomal aberrations induced in vivo can be reliably detected and quantified in a single cell type. Lung cells were isolated and cultured from Chinese hamsters that had been exposed to model mutagenic carcinogens, and then analysed in culture for genetic alterations. Chromosomal aberrations were assayed by the frequency in micronuclei found in binucleate cells after growth in the presence of cytochalasin B. Mutations were assayed by the frequency of thioguanine-resistant colonies on the 10th day of culture. X-rays and ethyl nitrosourea produced detectable increases in both mutations and chromosomal aberrations. Ethyl methanesulphonate produced large numbers of mutations but no chromosomal aberrations and methyl methanesulphonate produced the inverse: large numbers of chromosomal aberrations but no mutations. Our experience with these agents and the procedure suggests a standard protocol for the assay, and confirms the value of measuring both gene mutations and chromosomal aberrations.