Inhibitory effects of low doses of melatonin on induction of preneoplasticliver lesions in a medium-term liver bioassay in F344 rats: relation to the influence of electromagnetic near field exposure

We have previously reported that exposures of F344 male rats to both 900 MH z and 1.5 GHz electro-magnetic near fields (EMFs) results in slightly decre ased numbers and areas of glutathione S-transferase (GST-P)-positive liver foci, liver preneoplastic lesions in rats, in a medium-term liver bioassay (K. Imaida, M. Taki, T. Yamaguchi, T. Ito, S. Watanabe, K. Wake, A. Aimoto, Y. Kamimura, N. Ito, T. Shirai, Lack of promoting effects of the electroma gnetic near-field used for cellular phones (929.2 MHz) on mt liver carcinog enesis in a medium-term liver bioassay, Carcinogenesis 19 (1998) 311-314; K . Imaida, M. Taki, S. Watanabe, Y. Kamimura, T. Ito, T. Yamaguchi, N. Ito, T. Shirai, The 1.5 GHz electromagnetic near-field used for cellular phones does not promote rat liver carcinogenesis in a medium-term liver bioassay, Jpn. J. Cancer Res. 89 (1998) 995-1002.). In both experiments, the melatoni n serum levels were significantly decreased in both 900 MHz and 1.5 GHz exp osed groups as compared with sham-exposed control group values. Therefore, changes of serum melatonin levels may modify the development of preneoplast ic lesions in the livers of rats exposed by EMF. In order to clarify this q uestion, the effects of different doses of melatonin (1, 5, 10 and 20 ppm i n the drinking water) were analyzed in the same bioassay system employed fo r our previously reported EMF exposure studies. Six-week-old male F344 rats were given a single dose of diethylnitrosamine (DEN, 200 mg/kg b.w., i.p.) . Starting 2 weeks later, they were treated with 0, 1, 5, 10 and 20 ppm mel atonin in their drinking water for 6 weeks. Melatonin treatment were perfor med only during the night (between 18:00 to 09:00) in order to maintain the ir circadian rhythm, since serum melatonin levels are high at midnight. At week 3, all rats were subjected to a two-thirds partial hepatectomy. At wee k 8, the experiment was terminated and the animals were sacrificed. Serum h ormone levels of melatonin, adrenocorticotropic hormone (ACTH), corticoster one, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testo sterone at this time point were measured, only the first being elevated, wh ile LH and testosterone were reduced. Although clear dose dependence was no t apparent, both numbers and areas of GST-P-positive foci in the liver were decreased in the melatonin treated groups, this being significant for numb ers in the 10 ppm melatonin group. Comparison of the current results with t he previously reported findings for EMF exposure experiments, suggests that increase in melatonin serum levels is a possible reason for the associated tendency for decreased preneoplastic hepatocyte foci development. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.