Current genetic assays in long term protocols.

Abstract

Incorporation of mutagenicity tests in long term bioassays contributes relevant data for characterizing the oncogenic potential of a test compound. Additionally, genetic insult occurring in the germ cells may result in reproductive failure or the damage may be fixed as an inherited mutation with consequences in future generations. Tissues from animals necropsied at intervals throughout a study can be evaluated for chromosome damage and DNA perturbation. Comparatively non-invasive methods of collecting body fluids for developing a clinical chemistry profile also provide samples of blood for chromosome analysis, sister chromatid exchange or unscheduled DNA synthesis, or urine and feces to identify mutagenic excretory products in the Ames test. Such monitoring techniques can be employed in continuously treated animals and in animals set aside for recovery. Identification of genotoxic or non-genotoxic steps in carcinogenic activity in a variety of target organs provides insight into the mechanism of action of a test compound and may have implications for human risk assessment and regulation.