CARCINOGENICITY OF NITROPYRENES IN THE NEWBORN FEMALE RAT

The carcinogenicities of 1-nitropyrene (1-NP), 4-nitropyrene (4-NP), 1 ,3-dinitropyrene (1,3-DNP), 1,6-dinitropyrene (1,6-DNP), 1,8-dinitropy rene (1,8-DNP), 3-hydroxy-1-nitropyrene (3-OH-1-NP) and a mixture of 6 - and 8-hydroxy-1-nitropyrene (6/8-OH-1-NP) were investigated in newbo rn female rats. Newborn female CD rats were treated s.c. eight times a t weekly intervals with a total dose of 6.3 mu mol 1-NP, 1,3-DNP, 1,6- DNP or 1,8-DNP; control animals received only dimethylsulfoxide (DMSO) . The experiment was terminated at 67 weeks. With the exception of 1,6 -DNP- and 1,8-DNP-treated animals, which had average survival periods of 149 and 164 days respectively, the animals administered the other c ompounds did not show decreased survival. Malignant fibrous histiocyto mas were observed in 12%, 100% and 100% of the rats treated with 1,3-, 1,6- and 1,8-DNP respectively. Leukemia was found in 20% and 22% of t he animals treated with 1,6- and 1,8-DNP respectively. No control rats developed these tumors. Additionally, mammary tumors were induced in rats treated with 1-NP. Newborn female CD rats were similarly treated with 1-NP, 4-NP, 3-OH-1-NP, 6/8-OH-1-NP or DMSO and newborn female F34 4 rats were treated with 1-NP or DMSO. The experiment was terminated a t 86 weeks. 1-NP and 4-NP produced mammary adenocarcinoma in CD rats. Although 1-NP did not produce mammary adenocarcinoma in F344 rats, it induced leukemia. 4-NP also induced malignant fibrous histiocytomas in Co rats. This study demonstrates that 4-NP is more carcinogenic than 1-NP and that CD rats are more susceptible than F344 rats to mammary c arcinogenesis by 1-NP. Additionally, 1,6- and 1,8-DNP are more potent than 1-NP in inducing malignant fibrous histiocytomas and leukemia.