When Sugimura and associates discovered that the surfaces of fried meat and fish contained powerful mutangens, we developed the working hypothesis that there these mutagens may have adverse toxic effects for humans and may represent the genotoxic agents associated with specific diseases including certain of the important nutritionally-linked cancers. Methods were developed to separate and isolate these mutagens from fried meat, and together with Sugimura's group, we have identified a number of these chemicals. They are new types of heterocyclic amine similar to 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). IQ and related compounds are among the most powerful mutagens known in the Ames Salmonella typhimurium test system. We have begun to test their capabilities to induce DNA repair in hepatocytes in the Williams' test system and found IQ positive. In general, chemicals that are positive both in the Ames test and the Williams test are found to be carcinogenic. As part of the research plan, tests are in progress and others are to be carried out to determine whether IQ is carcinogenic, what the relative potency is under a given protocol compared to a suitably selected positive control carcinogen, and what the primary target organs are. A test in mice in Japan showed what IQ can induce neoplasms in the forestomach, liver, and lungs. A limited bioassay in our Institute supported by this grant currently underway indicates that IQ can induce mammary gland neoplasma in female Sprague Dawley rats, as does the positive control 4-aminobiphenyl. It is urgent to perform additional bioassays of IQ under standard conditions with the aim of acquiring essential data on the extent and scope of the carcinogenicity of IQ. Thus, IQ will be administered by gavage at 80 mg/kg (0.40 mmole/kg) twice weekly for 10 weeks, then once weekly for 40 weeks to male and female Fischer strain rats, that will continue on control diet for 28 weeks longer. The mammary gland, colon, and prostate carcinogen 2',3-dimethyl-4-aminobiphenyl at 20 mg/kg (0.10 mmole/kg) under identical protocols will be the positive control. These studies are designed to open a new field or research--that of the scope of action of new kinds of carcinogens widespread in the human food chain.
