mercaptopurine and Precancerous-Conditions

The modifying effects of an immunosuppressive agent, 6-mercaptopurine (6-MP), on development of focal lesions in liver cirrhosis models induced by carbon tetrachloride (CCl4) or furfural were studied in male F344 rats. Feeding of 6-MP at 50 p.p.m. for 20 weeks to animals with pre-existing liver cirrhosis caused immunosuppression, and significantly enhanced the induction of gamma-glutamyltranspeptidase (GGT)-positive foci and nodules in the CCl4 but not furfural case. Glutathione S-transferase P (GST-P)-positive preneoplastic lesions were not affected. Moreover, phenobarbital (PB) also enhanced the induction of GGT-positive hepatocellular lesions only in the CCl4-induced liver cirrhosis model, no promotion influence being exerted after treatment with the non-carcinogenic furfural. This study, therefore, suggests that 6-MP can enhance the induction of one type of preneoplastic foci and nodules and that essential differences exist between focal lesions arising in cirrhotic livers caused by CCl4 as opposed to furfural.

Topics: Alkaline Phosphatase; Animals; Aspartate Aminotransferases; Carbon Tetrachloride; Drug Synergism; Furaldehyde; gamma-Glutamyltransferase; Glutathione Transferase; Liver; Liver Cirrhosis, Experimental; Liver Neoplasms; Male; Mercaptopurine; Phenobarbital; Precancerous Conditions; Rats; Rats, Inbred F344

Carcinogenic and modification potential of 6-mercaptopurine (6-MP) was studied in a medium-term bioassay system for rat liver carcinogenesis. F344 male rats were initiated with a single dose (200 mg/kg body wt.) of diethylnitrosamine (DEN) i.p. and fed diets containing either 0.005% or 0.02% 6-MP with or without 0.05% phenobarbital (PB) for 6 weeks. Quantitative data revealed that 6-MP did not enhance the appearance of enzyme-altered preneoplastic foci and nodules even when administered at the highest dose (0.02%) despite showing an immunosuppressive effect and slight liver cell damage. Neither of the doses of 6-MP exerted any significant influence on the enhancing effect of PB when administered simultaneously in the medium-term-bioassay.

Topics: Animals; Body Weight; Diethylnitrosamine; Leukocyte Count; Liver Neoplasms, Experimental; Male; Mercaptopurine; Organ Size; Phenobarbital; Precancerous Conditions; Rats; Rats, Inbred F344

Topics: Anemia, Sideroblastic; Bone Marrow Examination; Cytarabine; Female; Humans; Immunodiffusion; Immunoelectrophoresis; Immunoglobulins; Iron; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Melphalan; Mercaptopurine; Middle Aged; Multiple Myeloma; Muramidase; Precancerous Conditions; Prednisone; Staining and Labeling; Vincristine

Topics: Antineoplastic Agents; Azathioprine; Condylomata Acuminata; Fluorouracil; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Mercaptopurine; Methotrexate; Papilloma; Pemphigus; Precancerous Conditions; Psoriasis; Scleroderma, Systemic; Skin Diseases; Skin Neoplasms; Virus Diseases