Induction of germline-length mutations at the minisatellites PC-1 and PC-2 in male mice exposed to polychlorinated biphenyls and diesel exhaust emissions.

PC-1 and PC-2 are hypervariable mouse minisatellites. The rates of spontaneous germline-length mutation have been shown to vary between different mouse strains. PC-1 is composed of GGCAG repeat units and PC-2 of GGCAGGA. Minisatellites frequently mutate by gaining or losing repeat units. Such length mutations in mini- and microsatellites have been associated with human disease and may therefore be an important endpoint in genetic toxicity testing. Carcinogenic activity of many chemicals is associated with their ability to induce heritable mutations. Since minisatellites are highly prone to mutate to new lengths, which can be assayed by Southern analysis, we used this method to detect heritable genetic effects in mice. Male mice exposed to diesel exhausts and/or polychlorinted biphenyls (PCB) were investigated for effects on the germline mutation frequenallele lengths in parents and offspring. For PC-1 significantly higher mutation frequencies were found in males treated with diesel exhausts + PCB (6 of 35 alleles) and with PCB alone (6 of 51 alleles) as compared to the males in the control group (0 of 43 alleles). The mutation frequency in the diesel exhaust group was not significantly increased (2 of 43 alleles). For PC-2 the only mutation found occurred in the PCB group (1 of 51 alleles). This in vivo study demonstrates--for the first time--chemically induced minisatellite mutations in the germline.