Carcinogenicities in mice and rats of IQ, MeIQ, and MeIQx

Abstract

The mutagenic heterocyclic amines, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) are present in broiled fish, fried beef, and beef extract. Their carcinogenicities in CDF1 mice and F344 rats were tested by their oral administration in the diet. In mice given diet containing 0.03% IQ, tumors developed in the liver (hepatocellular carcinomas or hepatocellular adenomas), forestomach (squamous cell carcinomas or papillomas), and lung (adenocarcinomas or adenomas) at high incidences. In mice given diet containing 0.04% or 0.01% MeIQ, squamous cell carcinomas and papillomas of the forestomach developed at high incidences. About 40% of the squamous cell carcinomas induced in the forestomach by 0.04% MeIQ metastasized to the liver. Clear dose-response relations were seen in the incidences of tumors in the groups given 0.04% and 0.01% MeIQ. The squamous cell carcinoma-papilloma ratios were higher in 0.04% groups than in 0.01% groups. Female mice treated with 0.04% and 0.01% MeIQ showed significantly higher incidences of liver tumors than controls. The experiment on the carcinogenicity of MeIQx at a dose of 0.06% in mice is still in progress but by experimental week 74, 4 of 16 males and 7 of 18 females autopsied were found to have liver tumors. Rats given diet containing 0.03% IQ showed high incidences of hepatocellular carcinomas, adenocarcinomas of the small and large intestines, and squamous cell carcinomas of the Zymbal gand, clitoral gland, and skin. Except for the liver, the target organs of IQ in CDF1 mice and F344 rats were different.