Tumor Target Organs and Rate of Survival in Long-living Transgenic Mice and their Parental Wild-type Counterparts Exposed to the Carcinogen Dimethylbenz(a)anthracene

Abstract

Two-year-old mice of the long-living transgenic mice of the αMUPA strain were previously found to show higher tumor resistance than the their initial wild-type (WT) strain (Tirosh, 2003). To better understand the mechanism underlying the differences in tumorigenesis rates between the two mouse lines, the rate of tumorigenesis and survival effects were studied in αMUPA mice and parental WT mice exposed to dimethylbenz(a)anthracene (DMBA). Each animal received three intragastric feedings of DMBA, each one week apart, at doses of 2, 1, and 1 mg dissolved in 0.2 ml corn oil; thus, the total amount of the carcinogen was 4 mg/mouse. Control mice received corn oil. The αMUPA mice exhibited distinctly higher survival rates in experimental chemically-induced tumorigenesis compared to their WT counterparts: 93% vs. 67%, p=2.7. The rate of tumorigenesis differed between the mouse lines (yield was 1.5 and 2.1), owing to a distinct tendency toward decreased tumor frequency in the skin and forestomach in the αMUPA mice. The experimental duration was also significantly higher for transgenic mice: 35.9±1.2 weeks compared to 30.5±1.3 weeks in WT mice, p<0.01. The lungs, forestomach and skin were target organs for the carcinogenic effect of DMBA. Our observations suggest that aging promotes the rate of spontaneous and induced tumorigenesis.