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...

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Published in:Carcinogenesis (New York) 1989-07, Vol.10 (7), p.1285-1290
Main Authors: Iwagawa, Masanori, Maeda, Toshiharu, Izumi, Keisuke, Otsuka, Hisashi, Nishifuji, Keiko, Ohnishi, Yoshinari, Aoki, Shigenobu
Format: Article
Language:English
Subjects:
Animals
Benzo(a)pyrene - toxicity
Biological and medical sciences
Body Weight - drug effects
Carcinogenesis, carcinogens and anticarcinogens
Carcinogens - toxicity
Carcinoma, Squamous Cell - chemically induced
Carcinoma, Squamous Cell - pathology
Chemical agents
Dose-Response Relationship, Drug
Lung - drug effects
Lung - pathology
Lung Neoplasms - chemically induced
Lung Neoplasms - pathology
Male
Medical sciences
Neoplasms, Experimental - pathology
Pyrenes - toxicity
Rats
Rats, Inbred F344
Reference Values
Tumors
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Summary: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 tumours induced by 1, 6-DNP were undifferentiated neoplasms, whereas most of those induced by BaP were well-differentiated squamous cell carcinomas.
ISSN:0143-3334
1460-2180
DOI:10.1093/carcin/10.7.1285