The tumor promoting effect of constant light exposure on diethylnitrosamine-induced hepatocarcinogenesis in rats.

Abstract The hypothesis that light-induced circadian clock suppression exerts a promoting effect on liver carcinogenesis was investigated in rats. Sixty-five male Wistar rats were given diethylnitrosamine (DEN, 10 mg/kg/day p.o.) for 6 weeks and were randomized into 3 groups. Rats from group 1 (N = 20) received DEN only. Rats from group 2 (N = 22) also received phenobarbital (pheno, 30 mg/rat/day p.o.) for 4 weeks as a promoting agent and rats from group 3 (N = 23) were exposed to continuous light. Three months after starting DEN treatment, urinary 6-sulfatoxymelatonin (αMT6s) excretion, a marker of circadian clock function, had lost its circadian rhythmicity in the LL group, with a 4-fold lower 24h mean than that found in the LDpheno and LD groups (8.0 ± 3.2 ng ml , 33.6 ± 3.1 ng ml and 34.3 ± 2.4 ng ml respectively; p from ANOVA χ 2 = 0.1). Nodules were more numerous and larger both in the LL group and in the LDpheno one as compared to the LD group (p from χ 2