Comparative dose-response study on the pulmonary carcinogenicity of 1, 6-dinitropyrene and benzo[a]pyrene in F344 rats

The dose dependencies of the lung carcinogenicity of 1, 6-dinitropyrene(1, 6-DNP) and benzo[a]pyrene (BaP) were examined by directinjections of these compounds into rat lungs. A total of 276male F344 rats were divided into 10 groups and given variousdoses of 1, 6-DNP or BaP, or no drug (control group). Both chemicalswere injected into the lung, as suspensions in beeswax-tricaprylinand the animals were then observed for 104 weeks. The incidencesof lung cancer were 0/39 (0%), 4/30 (13%), 13/31 (42%), 22/26(85%) and 6/9 (67%) in groups treated with 0.003, 0.01, 0.03,0.1 and 0.15 mg of 1, 6-DNP respectively, and 1/29 (3%), 7/30(23%) 22/29 (76%) and 9/13 (69%) in those treated with 0.03,0.1, 0.3 and 1.0 mg of BaP respectively. No lung cancer wasfound in control rats. Thus the incidences of lung cancer inducedby 1, 6-DNP and BaP showed significant dose dependence. At equaldoses, the incidence of lung cancer was much higher with 1,6-DNP than with BaP, and the induction of cancer by 1, 6-DNPwas higher even at one-third the dose of BaP. Histologically,most tumours induced by 1, 6-DNP were undifferentiated neoplasms,whereas most of those induced by BaP were well-differentiatedsquamous cell carcinomas.