Susceptibility to spontaneous mammary carcinogenesis in mice of the CBi stock

SUÁREZ, C.; RENATA, L.; MARGARITA ISABEL PIAZZON; HINRICHSEN, L.

Washington, DC

Congreso; 006 AACR Annual Meeting . Proceedings of the American Association for Cancer; 2006

Susceptibility to mammary cancer development is a complex character under polygenic control. Susceptibility to mammary carcinogenesis was analyzed in lines CBi+ and CBi/C of the CBi stock and their reciprocal F1 crosses, to determine whether the genotype modulates expression of the character. These lines, currently in their 95th generation of selective breeding (theoretical inbreeding coefficient > 0.98), were obtained by disruptive selection for body conformation; the base population from which they derive was formed in 1965 crossing mice from Balb, Rockland, NIH and Swiss strains; it was outbred until 1978, when the selection experiment begun. Mammary tumor development was monitored weekly by palpation in CBi+, CBi/C and F1 females, and its size measured. General health status was examined bi-weekly and mice were sacrificed when the tumor reached the maximum permitted size, signs of physical deterioration appeared or weight loss was 30%; the remaining mice were sacrificed at 600 days of age. Tumors were processed for histology. Age at tumor detection was analyzed by the Kaplan-Meier method, and differences in the proportion of animals with tumors with the P2 test. T-cell clone deletion of lymphocytes from milk-borne MMTV-free Balb/c fostered by CBi+ were analyzed by flow cytometry. The results are shown below: CBi+ F1 CBi/C (+ x C) (C x +) Age at tumor detection (median, days) 243a 311a 401b 504c % of mice with tumor (mice with tumors/total studied) 100a (39/39) 96a (23/24) 77b (17/22) 17c (6/36) Values with different superscript differ at 0.01 Balb/c fostered by CBi+ showed deletion of Sag-cognate Vb14+ T cells. The differential behavior of the reciprocal F1s suggests that additional genetic factors interact with the exogenous MMTV and contribute to CBi+ susceptibility.