During the past ten years the only new chemicals introduced in the monkey colony were heterocyclic amines found in cooked meat, i.e. 2-amino-3- methylimidazo-[4,5-f]quinoline (IQ), 2-amino-3,8-dimethylimidazo[4,5- f]quinoxaline (8-MeIQx), and 2-amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (PhIP). Dosing of forty monkeys with IQ was started in 1985. Eighty percent of the twenty animals dosed 20 mg/kg orally five times per week (average latent period 42.4 m), and 40% of the animals dosed with 10 mg/kg (average latent period 58.5 m) have developed hepatocellular or mixed hepatocellular and cholangiocarcinomas. So far, there is no evidence of tumor development in the monkeys dosed with 8-MeIQx (since 1987) and PhIP (since 1990). A histopathological study of hearts from immediate autopsies of monkeys chronically dosed with IQ revealed focal myocyte degeneration and mitochondrial abnormalities. To further examine the possibility of IQ-induced myocardial damage, the effect of IQ and its metabolites on cardiac myocytes is being assessed in a cell culture system. Studies of IQ metabolism in monkeys suggested that N-hydroxy- lation of IQ plays a role in the initiation of the hepatocarcinogenic process. Other ongoing studies include: 1) evaluation of p53 suppressor gene mutations in carcinogenically-induced tumors, using PCR amplified DNA; 2) examination of IQ-induced tumors for mutations in oncogenes and suppressor genes; 3) formation and repair of DNA adducts in tissues and white blood cells in monkeys dosed with IQ and PhIP, as well as DNA repair in specific genes; 4) accelerator mass spectrometric studies on the metabolism of hamburger equivalent doses of PhIP.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CP003509-29
Application #
3838297
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
29
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Division of Cancer Epidemiology and Genetics
Department
Type
DUNS #
City
State
Country
United States
Zip Code