The carcinogenic risk of aromatic
amines in humans was first discovered when a physician related the occurrence of
urinary bladder cancer to the occupation of his patients. They were employed in the dyestuff industry, chronically exposed to large amounts of intermediate arylamines. Laboratory investigations disclosed that rats and mice administered specific
azo dyes arylamines or derivatives developed
cancer, primarily in the liver. Also, at that time, a possible
pesticide,
2-aminofluorene, was tested for chronic toxicity, revealing that it rapidly induced
cancers in several organs of rodents. This led to investigations on the mode of action of this class of chemicals, including their metabolic conversion. Biochemical activation to more reactive N-hydroxy compounds was found to occur, mostly in the liver, through what is now known as the
cytochrome p450 enzyme systems, and also through
prostaglandin synthetases. There were species differences. Guinea pigs were resistant to
carcinogenesis because of the low titer of the necessary activating
enzymes. In target tissues, a second essential reaction was necessary, namely acylation or
sulfate ester formation. The reactive compounds produced display attributes of genotoxicity in appropriate test systems. Interest in this class of compounds increased when of Sugimura and colleagues discovered the formation of
mutagens at the surface of cooked meat or fish, that were identified as heterocyclic
amines (HCAs). These compounds undergo the same type of activation reactions, as do other arylamines. Epidemiological data suggest that meat eaters may have a higher risk of breast and
colon cancer. HCAs induced
cancer in rats in these organs and also in the prostate and the pancreas. In addition, there is some evidence that they affect the vascular system. The formation of HCAs during cooking can be decreased by natural and synthetic
antioxidants, by
tryptophan or
proline, or by removing the essential
creatine through brief microwave cooking prior to frying or broiling. The amounts of HCAs in cooked foods are small, but other components in diet such as omega-6-polyunsaturated
oils have powerful promoting effects in target organs of HCAs. On the other hand, the action of HCAs may be decreased by foods containing
antioxidants, such as vegetables, soy, and
tea. Some constituents in foods also induce phase II
enzymes that detoxify reactive HCA metabolites. Additional mechanisms involved decreased growth of
neoplasms by intake of protective foods. Possibly, the carcinogenic effect of HCAs is accompanied by the presence of
reactive oxygen species (ROS), which are also inhibited by
antioxidants. World-wide, there have been many contributors to knowledge in this field. Adequate information may permit now to adjust lifestyle and lower the risk of human disease stemming from this entire class of aryl and HCA.