Long-term carcinogenicity of pan masala in Swiss mice

Carcinogenicity of pan masala, a dry powdered chewing mixture of areca nut, catechu, lime, spices and flavoring agents was evaluated by means of the l ong-term animal bio-assay 6- to 7-week old male and female S/RVCri mice wer e divided randomly into intermediate and lifetime exposure groups and fed n ormal diet without pan masala-(zero dose) or diet containing 2.5% and 5% pa n masala. Animals in the intermediate-exposure group(n = 10/gender/dose gro up) were killed after 6, 12 or 18 months of treatment, while those in the l ifetime-exposure group (n = 54/gender/dose group) were killed when moribund or at the termination of the experiment at 24 months. Several tissues were processed for histopathological examination. The body weight and survival rate of mice fed pan masala were lower than that of the controls. Histopath ological observations of tissues from control animals did not reveal any ne oplastic alterations. However, lifetime feeding of pan masala induced adeno ma of the liver, stomach, prostate and sebaceous glands, also forestomach p apilloma, liver hamartoma, hepatoma and hemangioma, carcinoma of the forest omach, adenocarcinoma of the lung and liver, and testicular lymphoma. Neopl astic lesions appeared mainly in the liver (n = 13), stomach (n = 3) and lu ng(n = 8). Lung adenocarcinoma, the most frequent malignant tumor type, was observed in 2/120 mice in the intermediate-exposure group and in 8/216 ani mals in the lifetime-exposure group. Statistical analysis of tumor-inductio n data revealed a significant dose-related increase in lung adenocarcinomas but not in liver and stomach neoplasms indicating that lung is the major t arget tissue for the carcinogenic action of pan masala. (C) 1999 Wiley-Liss , Inc.