The tumor promoting effect of constant light exposure on diethylnitrosamine-induced hepatocarcinogenesis in rats
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) recei...
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Published in | Life sciences (1973) Vol. 64; no. 26; pp. 2523 - 2534 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Netherlands
Elsevier Inc
1999
|
Subjects | |
Online Access | Get full text |
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Summary: | 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 < 0.001). Laparotomy was then performed. The proportion of rats with macroscopic nodules on liver surface was 72% (LD group), 89% (LDpheno group) and 95% (LL group) (p from
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 < 0.05). All the rats died with hepatocellular carcinomas, with a median survival of 5 months, similar in all 3 groups. Light-induced circadian clock suppression exerted a promoting effect similar to that caused by phenobarbital in this model, yet through different effects on circadian system function. |
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ISSN: | 0024-3205 1879-0631 |
DOI: | 10.1016/S0024-3205(99)00210-6 |