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 direct injections of these compounds into rat lungs. A total of 276 male F344 rats were divided into 10 groups and given various doses of 1,6-DNP or BaP, or no drug (control group). Both chemicals were injected into the lung, as suspensions in beeswax--tricaprylin and the animals were then observed for 104 weeks. The incidences of 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 was found in control rats. Thus the incidences of lung cancer induced by 1,6-DNP and BaP showed significant dose dependence. At equal doses, the incidence of lung cancer was much higher with 1,6-DNP than with BaP, and the induction of cancer by 1,6-DNP was higher even at one-third the dose of BaP. Histologically, most tumors induced by 1,6-DNP were undifferentiated neoplasms, whereas most of those induced by BaP were well-differentiated squamous cell carcinomas.
Iwagawa
M
M
Second Department of Pathology, School of Medicine, University of Tokushima, Japan.
Maeda
T
T
Izumi
K
K
Otsuka
H
H
Nishifuji
K
K
Ohnishi
Y
Y
Aoki
S
S
D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D008168:Lung / Q000187:drug effects / Q000473:pathology*; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D009374:Neoplasms, Experimental / Q000473:pathology; D011721:Pyrenes / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D012016:Reference Values
D002273:Carcinogens; D011721:Pyrenes; D001564:Benzo(a)pyrene; C033309:1,6-dinitropyrene