Time and dose dependence of acceptance of UV-induced syngeneic tumor implants in chronically UV-exposed hairless mice

Abstract

The kinetics of skin cancer induction by UV radiation has been extensively studied in hairless mice and described by Weibull statistics in which the time till 63% of the mice bear tumors is a primary parameter. However, the kinetics of the associated immunosuppression remained to be determined. To this end, we implanted a syngeneic UV-induced skin carcinoma cell line (T51/6.53) in the ventral skin of HRA/SKH hairless mice after various periods of daily dorsal UV exposure, either 150 or 75 mJ/cm2 per day UV from F40 sunlamps (regimens that when continued yield 63% of the mice with 1 mm tumors in 11.5 or 16.2 weeks, respectively). Both exposure regimens achieved a 100% acceptance (after 7 and 16 weeks, respectively). The implants failed to grow in all unirradiated control mice, but the percentage of mice in which the implants grew increased with the UV treatment time and dose. The estimated times to 63% implant acceptance were 4.3 ± 0.8 and 8.2 ± 0.8 weeks for the high and low daily doses, respectively. As reported earlier for shaved haired mice, there appears to be a straight reciprocity between daily UV dose and the time to tumor acceptance, i.e. the latter fully depends on the cumulative UV dose, whereas the tumor induction does not. The latter probably also depends on a pure elapse of time, i.e. UV-independent processes. A further analysis of the Weibull description indicates that immunosuppression toward the tumor requires fewer UV-driven steps than tumor induction.