metanil-yellow and Precancerous-Conditions

Metanil yellow (MY) and malachite green (MG) are textile dyes, which, despite the ban occurs unsrupulously as food colouring agents. Accordingly they constitute a serious public health hazard and are of sufficient environmental concern. We have earlier reported that both MY and MG have tumor enhancing effects on the development of hepatic preneoplastic lesions induced by N-nitrosodiethylamine in rats. In order to understand the possible mechanisms by which MY and MG enhance tumor development, in this study we have tested the effects of MY and MG on DNA synthesis and PCNA expression in preneoplastic hepatic lesions during N-nitrosodiethylamine (DEN) induced hepatocarcinogenesis in male Wistar (WR) rats. Rats were administered 200 ppm DEN through drinking water for a period of one month. Administration of DEN for a period of one month showed an upregulation of cell cycle regulatory proteins namely cyclin D1, CDK4, cyclin E and CDK2. Accordingly, in other experiments, the animals were further administered MY and MG for a period of one month following one month DEN treatment. The effects of MY and MG were monitored on the basis of cell proliferation markers--DNA synthesis and PCNA expression both by immunohistochemical and immunoblotting. Following DEN administration, MY, MG and PB showed stimulation of DNA synthesis and increased PCNA expression when compared with either the corresponding controls or only DEN treated animals. In the present study, enhancing effect of MY, MG and PB on the cell proliferation markers during DEN-induced hepatic preneoplasia in rats was observed.

Topics: Animals; Azo Compounds; Blotting, Western; Cell Division; Coloring Agents; Cyclins; Diethylnitrosamine; DNA, Neoplasm; Dose-Response Relationship, Drug; Drug Synergism; Immunoenzyme Techniques; Liver Neoplasms, Experimental; Male; Precancerous Conditions; Proliferating Cell Nuclear Antigen; Rats; Rats, Wistar; Rosaniline Dyes; Thymidine

Metanil yellow (MY) and Malachite green (MG) are textile dyes, which, despite the ban, occur unscrupulously as food colouring agents. Accordingly they constitute a serious public health hazard and are of sufficient environmental concern. We have earlier reported that both MY and MG have tumor promoting effects on the development of hepatic preneoplastic lesions induced by N-nitrosodiethylamine in rats. In order to understand the possible mechanism(s) by which metanil yellow (MY) and malachite green (MG) promotes liver tumor development, we have studied the tyrosine phosphorylation and protein phosphatases during tumor promotion. We have also investigated the possible overexpression of G1/S cyclins and PCNA during tumor promotion by MY and MG. The present investigation indicates that enhanced tyrosine phosphorylation is associated with no change in levels of tyrosine protein phosphatases. We have also observed an increase in the expression of PCNA and G1/S cyclins during tumor promotion. These factors collectively may contribute to the abnormal cell proliferation during tumor promotion by MY and MG.

Topics: Animals; Azo Compounds; Cyclins; Diethylnitrosamine; Food Coloring Agents; G1 Phase; Liver Neoplasms, Experimental; Male; Phosphorylation; Precancerous Conditions; Proliferating Cell Nuclear Antigen; Rats; Rosaniline Dyes; S Phase; Tyrosine

The dose-dependent effect of mentanil yellow (MY) on the development of preneoplastic hepatic lesions during N-nitrosodiethylamine (DEN) induced hepatocarcinogenesis was studied in comparison with phenobarbitone (PB), in male Wistar (WR) rats. Rats were administered 200 ppm DEN through drinking water for a period of 1 month. After an interval of 2 wk, the animals were administered MY at concentrations of 0.1, 0.5 and 1.0 per cent in the diet for a period of 7 months. PB at 500 ppm served as the standard tumour promoter. The dose-dependent tumour promoter effects of MY were monitored on the basis of morphological appearance of the livers, liver weight profile, histological pattern, appearance of gamma-glutamyl transpeptidase (GGT) positive foci, total GGT activity and the induction of glycogen-deficient islands. All the three doses of MY were found to enhance liver carcinogenesis when compared with either the corresponding controls or only the DEN treated animals. MY at 0.1 per cent was found to be more effective as an enhancer of DEN-induced carcinogenesis than 0.5 and 1.0 per cent. In the present study a dose-related enhancing effect of MY on DEN-induced hepatic preneoplasia in rats has been demonstrated.

Topics: Animals; Azo Compounds; Carcinogens; Diethylnitrosamine; Dose-Response Relationship, Drug; Food Coloring Agents; Liver Neoplasms; Male; Precancerous Conditions; Rats; Rats, Wistar