Effects of melatonin on N-nitroso-N-methylurea-induced carcinogenesis in rats and mutagenesis in vitro (Ames test and COMET assay)

The effect of melatonin, an indole hormone of the pineal gland, on the init iation of N-nitroso-N-methylurea (NMU)-induced carcinogenesis in rats and m utagenesis in vitro has been investigated. Two-month-old female LIO rats (g roups 1 and 2) were exposed to a single injection of NMU (50 mg/kg of body weight, i.v.). Rats from group 2 were given melatonin orally (20 mg/l) from 18:00 to 09:00 h over 3 days (2 days before and 1 day after NMU injection) . Animals from group 1 (control) were administered the solvent (ethanol/wat er, 1:1000). Rats were followed up to natural death or were sacrificed when moribund. Tumors developed both in rats treated with NMU alone (50.0%) and in rats exposed to NMU plus melatonin (34.8%). The percentage of malignant tumor-bearing rats in group 2 (21.7%) was lower (P < 0.02) than that in th e other group (41.7%). Melatonin also decreased the multiplicity of maligna nt tumors 1.3-fold and reduced the incidence of malignancies in some organs . Two in vitro tests were used for mutagenesis studies: the Ames test (stra ins TA 100 and TA 102 of Salmonella typhimurium) and the Single Cell Gel El ectrophoresis assay (SCGE assay or COMET assay) performed on CHOK1 cells. M elatonin itself revealed no genotoxic effect in either of the tests. No pro tective action of melatonin (at doses of up to 2 mu mol/plate) towards NMU was found in the Ames test, In contrast, in the SCGE assay a slight, but st atistically significant (P < 0.001), dose-related anticlastogenic effect of melatonin (10(-10)-10(-7) M) was observed. Thus, our data indicate that me latonin may act as an anti-initiating hormone in NMU-induced carcinogenesis and possess anticlastogenic activity towards NMU in CHOK1 cells. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.