The induction of a mutator phenotype has been hypothesized to cause the accumulation of multiple mutations in the development of cancer.
Recent evidence suggests that the mutator phenotype is associated with DNA repair deficiencies.
We have been using a challenge assay to study exposed populations to test our hypothesis that exposure to environmental toxicants can induce DNA repair deficiency in somatic cells. In this assay, lymphocytes were irradiated in vitro to challenge cells to repair the radiation-induced DNA strand breaks. An increase of chromosome aberrations in the challenged cells from toxicant-exposed populations compared to nonexposed populations is used to indicate abnormal DNA repair response. The phenomenon was also demonstrated using experimental animals. These challenged lymphocytes showed an MNNG dose-dependent increase of abnormal DNA repair response.