The comparative carcinogenicities of N-hydroxy-N-acetyl-1-aminopyrene,
N-acetyl-1-aminopyrene, and 1-, 2-, and
4-nitropyrene were determined following i.p. injection into weaning female CD rats (67 mumol/kg
body weight in
dimethyl sulfoxide; 3 times/week for 4 weeks). At sacrifice 61 weeks after the first injection the incidences of malignant mammary
tumors were increased significantly to 45 and 24% in the 4-nitropyrene- and N-hydroxy-N-acetyl-2-aminofluorene-treated groups, respectively. Cellular altered foci in the liver were increased significantly in the N-acetyl-1-aminopyrene-, N-hydroxy-N-acetyl-1-aminopyrene-, and N-hydroxy-N-acetyl-2-aminofluorene- treated groups; the latter two compounds also led to significantly increased formation of hyperplastic nodules in this organ. Significant increases in
leukemia induction were observed in animals treated with
2-nitropyrene or N-hydroxy-N-acetyl-2-aminofluorene. In an experiment designed to compare the influence of the route of administration on the carcinogenic potential of this agent,
1-nitropyrene was injected i.p. or s.c. into weanling female CD rats (100 mumol/kg
body weight; once a week for 4 weeks). The animals were sacrificed at 87 to 90 weeks after the first treatment. The incidences of mammary gland
tumors in animals receiving
injections of
1-nitropyrene by either route (59%) were significantly higher than in
solvent-injected controls (37%). The incidences of
adenocarcinoma in the i.p.
1-nitropyrene group (28%) and
fibroadenoma in the s.c.
1-nitropyrene group (52%) were significantly higher than in the control animals (7 and 27%, respectively). These data suggest that the demonstration of the weak carcinogenicity of
1-nitropyrene is probably more a function of the length of the observation period than of the routes of administration used here. A further exploration of the effect of the route of administration involved treatment of weanling female CD rats by direct injection of 1-, 2-, or
4-nitropyrene into the mammary fat pads. A total of 2.04 mumol of the nitrocompound in
dimethyl sulfoxide was injected into the mammary glands under each of the 6 left nipples. The right mammary glands were treated with the
solvent only.
Injections of the thoracic nipple areas were carried out on day 1; inguinal areas were treated on day 2. The animals were sacrificed after 77 weeks. The number of mammary
tumor-bearing animals (23 of 28), the number with
fibroadenoma (15 of 28), and the number with
adenocarcinoma (19 of 28) were significantly increased in the 4-nitropyrene-treated group as compared with animals treated with only
dimethyl sulfoxide.(ABSTRACT TRUNCATED AT 400 WORDS)