Cynomolgus monkeys chronically treated with 2-amino-3-methylimidazo[4,5- f]quinoline (IQ) for carcinogenicity testing revealed evidence of myocyte necrosis with and without associated inflammation, myocyte hypertrophy, myofibrillar loss and mitochondrial abnormalities. These findings raised the question of whether heterocyclic arylamines (HAAs) in cooked meats could be associated with idiopathic cardiomyopathies. Thus, it was of interest to develop models to investigate heterocyclic amine cardiotoxicity. Primary cultures of fetal myocytes were exposed to the activated forms of the carcinogens N-hydroxy-IQ and N-hydroxy-PhIP. LDH leakage increased in proportion to the carcinogen dose but was signifi- cantly greater in cells exposed to N-hydroxy-IQ than in cells exposed to N-hydroxy-PhIP. Electron microscopy revealed that treated cells had swollen and irregular mitochondria and fewer organelles. However, DNA adducts, assessed using the 32-P-postlabeling method, were significantly higher in myocytes exposed to N-hydroxy-PhIP than in cells exposed to N- hydroxy-IQ. The toxic effects of heterocyclic arylamines were also evaluated in rats given IQ or PhIP (100 mg/kg, p.o. 10x). Light micro- scopic and ultrastructural cardiac abnormalities were present in seven of eight rats exposed to IQ or PhIP. Whereas control animals had a normal cardiac morphology, carcinogen-treated animals had foci of chronic inflammation with myocyte necrosis, myofibrillar dissolution and disarray, and dilation of T-tubules. These results suggest that, in addition to being carcinogenic, food mutagens may play a role in cardiac degeneration.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CP005749-01
Application #
3774934
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Division of Cancer Epidemiology and Genetics
Department
Type
DUNS #
City
State
Country
United States
Zip Code