Modeling of Periodically Changing Predictable Response to Mutagens in Successive Inbred Generations of CBA/LacY Mice

A hypothesis on the genetic determination of periodic fluctuations of the sensitivity to the mutagen thioTEPA in successive inbred generations of mice has been earlier put forward. This study was the initial stage of testing this hypothesis. The mouse strain CBA/LacY was divided into two substrains, which differed in the rate of generation change. As a result, two colonies of isogenic mice differing by 10–12 generations with respect to the inbred age will be obtained. Both the rate and range of variations in the mutagen sensitivity (four generations per period of the cycle and 20–40% of cells with chromosome aberrations after the standard dose of 2.5 mg/kg of thioTEPA, respectively) in 19 generations of the fast substrain agreed with earlier data. The response of the slow substrain corresponded to the expected response of the fast substrain after the given number of generations. In the mice of generations F₁₄₂and F₁₄₆that lived simultaneously and differed in thioTEPA sensitivity, the effects of the carcinogen benzoa]pyrene (BaP) were significantly different. The levels of these effects corresponded to the levels of the responses to thioTEPA. The data obtained agree with the hypothesis tested.