Effects of deficiency in p53 or bcl-2 on the sensitivity of clonogenic cells in the small intestine to low dose-rate irradiation

Purpose: To study the rule of p53 and bcl-2 in the response of the small in testine to irradiation delivered at low dose-rate. Materials and methods: Mice homozygous for p53 or bcl-2 deletion (- / -), t heir respective heterozygotes (+ / -), and their wild-type littermates (+ / +) including a previously used hybrid strain (B6D2F(1)), were irradiated t o the whole-body using Co-60 gamma-rays at 1 Gy h(-1). Crypt survival level s in the small intestine were measured at day 3 after the end of irradiatio n. Results: Crypt survival levels were higher in p53 - / - mice than in the ot her p53 genotypes after 25-30 Gy, but not after lower or higher doses. Simi lar experiments with the three genotypes for bcl-2 status showed lower cryp t survival after all doses used in the - / - mice, compared with the + / - and + / + mice, which were similar in response. The marked degree of curvat ure in the survival curve observed fur the p53 genotypes was also observed in B6D2F(1) hylrid mice, was particularly striking in the p53 -/- mice, but was not seen to the same extent in the bcl-2 genotypes. The heterozygotes for p53 or for bcl-2 were nearer in response to their respective + / + geno types rattler than the - / - genotypes. Conclusion: The increased crypt survival levels at some radiation dose leve ls in the p53 nulls contrasts with the lack of change I reported previously using irradiation at high dose-rate. The decreased survival in the bcl-2 n ulls is consistent with the known 'survival' function of bcl-2, although bc l-2 expression has not been detected immunohistochemically in this intestin al site. The marked degree of curvature in the dose-response curve at high dose levels For some genotypes was unexpected at this low dose-rate.