Carcinogenesis, Benzo[a]pyrene Metabolism, and Sister Chromatid Exchanges in Lungs of Rats After Intratracheal 3-Methylcholanthrene

Induction of squamous cell carcinomas in F344 rats by the intratracheal instillation of carrier-free 3-methylcholanthrene [(MCA) CAS: 56-49-5] was dependent on the total dose and on the size of the crystals. With the use of MCA particles of about 1 μm in mean diameter in doses up to 25 mg, delivered as 5 doses of 5 mg each at 2-week intervals, no tumors were produced. With particles in the range of 10–300 μm, all rats receiving 25 mg developed squamous cell carcinoma of the lung. At lower doses, the tumor incidence was dose-dependent. Metabolism of [3H]benzo[a]pyrene [CAS: 50-32-8] or [3H]MCA by microsomes from lungs and livers of treated rats was increased over that of controls and remained elevated for more than 6 weeks in the lung and 2 weeks in the liver. Repeated treatment of rats did not increase the levels of enzyme activity beyond that seen after a single treatment, nor did the increased activity persist longer than was seen after a single treatment. Sister chromatid exchanges (SCE) were measured in primary cultures of lung cells and in peripheral and spleen lymphocytes from treated rats. Elevated frequencies of SCE were found in lung cells up to 6 weeks following a single treatment with MCA. Repeated treatment did not increase the frequency or increase the persistence of the SCE. No increase in exchange frequency was found in lymphocytes of any treated rats.