Toxicity Studies on Carbon Tetrachloride and N-nitrosomethylurea Independently and in Combination in Rats*

This trial was designed to study the subchronic effects of carbon tetrachloride (CCl4) and N-Nitrosomethylurea (NMU) independently as well as in combination. In the CCl4 and CCl4 + NMU groups, the lipid peroxidation (LPO) recorded the peak level on the 15th day while in NMU group it was reached only on the 75th day. Serum gamma glutamyl transpeptidase (GGT) levels were higher on the 15th day in CCl4 group and on the 75 th day in NMU and CCl4 + NMU groups. Liver tissue GGT recorded the maximum level on the 15th day while it reached only by the 75th day in the NMU and CCl4 + NMU groups. DNA strand breaks recorded an increase on the 45th day in CCl4 group, 75 th day in the NMU group and from 45th day onwards in the CCl4 + NMU group. Initially there was cytoplasmic vacuolarity in the hepatocytes followed by cholangio-fibrosis while kidney revealed degenerative changes. Congestion and haemorrhages were seen in the stomach during the initial period of the trial in the CCl4 group. In the NMU group liver showed centrilobular necrosis, while kidney revealed tubular epithelial cytoplasmic vacuolations. Hyperplasia of squamous epithelium was seen in the stomach while testes showed degenerative changes. In the combined group, focal bile duct hyperplasia was prominent in the liver, while kidneys revealed glomerular swelling and exudation with degenerative changes in the tubules. Hyperplasia and hyperkeratosis were seen in the stomach while testes showed degenerative changes.