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

Citation
S. Van Den Heiligenberg et al., The tumor promoting effect of constant light exposure on diethylnitrosamine-induced hepatocarcinogenesis in rats, LIFE SCI, 64(26), 1999, pp. 2523-2534
Citations number
29
Categorie Soggetti
Biochemistry & Biophysics
Journal title
LIFE SCIENCES
ISSN journal
00243205 → ACNP
Volume
64
Issue
26
Year of publication
1999
Pages
2523 - 2534
Database
ISI
SICI code
0024-3205(19990521)64:26<2523:TTPEOC>2.0.ZU;2-E
Abstract
The hypothesis that light-induced circadian clock suppression exerts a prom oting effect on liver carcinogenesis was investigated in rats. Sixty-five male Wistar rats were given diethylnitrosamine (DEN, 10 mg/kg/da y 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 phenobar bital (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 (alpha MT6s) excretio n, a marker of circadian clock function, had lost its circadian rhythmicity in the LL group, with a 4-fold lower than 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 chi(2) = 0.1). no dules were more numerous and larger both in th LL group and in th LDpheno o ne as one compared to the LD group (p from chi(2) <0.05). All the rats died with hepatocellular carcinomas, with a median survival of 5 months, simila r in all 3 groups. Light-induced circadian clock suppression exerted a prom oting effect similar to that caused by phenobarbital in this model, yet thr ough different effects on circadian function.