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The carcinogenic potential of 2‐amino‐3‐methylimidazo[4,5f]quinoline (IQ) was evaluated in cynomolgus monkeys. Monkeys received IQ, beginning at the age of one year, at doses of 10 or 20 mg/kg by gavage. Thus far, IQ has induced hepatocellular carcinoma in three monkeys with a latent period of 27 to 37 months. Metastases to the lung occurred in two of the three monkeys. Microscopically, the hepatocellular carcinoma in all three cases demonstrated a trabecular pattern. These data demonstrate that IQ is a potent carcinogen in nonhuman primates and support the idea that it is a potential carcinogen for humans.

A system in which oral tissues of inbred F344 adult rats and Syrian golden hamster embryos were used in combination with autoradiography was developed for measurement of unscheduled DNA synthesis (UDS). For this, oral mucosa, submandibular gland, tooth germ and mandible in short-term organ cultures were treated with 4-nitroquinoline 1-oxide or N-methyl-N-nitrosourea plus (methyl-3H)thymidine. Significant numbers of silver grains, indicating UDS, were detected over the nuclei of cells of all these tissues except rat salivary gland after treatment with carcinogens. This autoradiographic method is suitable for detection of UDS in oral tissues in conditions mimicking those in vivo. Results obtained in this study indicated a potential use of this system for studies on the mechanism of carcinogenesis at a cellular level comparable to in vivo carcinogenesis studies on oral tissues.

Induction of liver tumors was studied in rats given carcinogens as follows: (1) N-nitrosodimethylamine (DMN) alone; (2) 4-dimethylaminoazobenzene (DAB) alone; (3) DMN followed by DAB; and (4) DAB followed by DMN. The main findings were: (1) DAB feeding for 0.62 to 2.5 months, followed by DMN feeding for 5 months, induced liver carcinomas more frequently than did DMN alone given for 5 to 10 months, or DAB alone given for 2.5 months. (2) Likewise, DMN feeding for 0.62 or 1.25 months, followed by DAB feeding for 5 months, induced liver carcinomas more frequently than did DMN alone given for 5 to 10 months or DAB alone given for 2.5 months. Interestingly, when DMN was given for a longer time (2.5 months), followed by DAB for 5 months, 50% of the induced liver tumors were non-epithelial. (3) Liver tumors were induced by sequential administration of the two carcinogens in doses that did not induce tumors when each carcinogen was given alone over a comparable time period. (4) The latent period for liver tumor development was shorter in groups that received the two carcinogens sequentially than in those that received DAB or DMN alone for comparable time periods.

The amount of DNA in cell nuclei was determined by microspectrophotometry on Feulgen-stained preparations using basal cells from the back skin of mice after painting with 3-methylcholanthrene (3-MC), croton oil and turpentine, and from skin after a burn. In the hyperplastic epithelium of the skin painted with 3-MC, the amount of DNA per cell nucleus was the same as that of normal skin but the mean amount of DNA in papilloma and atypical hyperplasia was slightly higher. However, no significant difference was found from that of the normal. In contrast to the above lesions, the amount of DNA in squamous cell carcinomas was elevated and the range of modal distribution was wider. In the hyperplastic epithelium induced by painting with croton oil or turpentine, the amount of DNA was also near the normal range. In the regenerating hyperplastic epithelium after a burn, the number of cells with an increased amount of DNA was higher for 2–5 days after the burn but no essential difference was observed from the normal.

The mutagenic compound, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), originally isolated from cooked beef, was tested for carcinogenicity in CDF1 mice of both sexes. When PhIP was given in the diet at a concentration of 0.04%, high incidences and early appearances of lymphomas were observed in both sexes during the 579-day experiment.