Tumor-initiating activity and carcinogenicity of dibenzo[a,l]pyrene versus 7,12-dimethylbenz[a]anthracene and benzo[a]pyrene at low doses in mouse skin.
Carcinogenesis
; 14(5): 875-8, 1993 May.
Article
em En
| MEDLINE
| ID: mdl-8504480
ABSTRACT
Dibenzo[a,l]pyrene (DB[a,l]P) is an extremely potent carcinogen that may be present in environmental samples. Dose-response studies were conducted at low doses in mouse skin by initiation-promotion and repeated application to compare its activity to that of 7,12-dimethylbenz[a]anthracene (DMBA), benzo[a]pyrene (B[a]P), DB[a,l]P-8,9-dihydrodiol and DB[a,l]P-11,12-dihydrodiol. Female SENCAR mice were initiated with 1 or 0.25 nmol of DB[a,l]P, DMBA, B[a]P or DB[a,l]P-11,12-dihydrodiol and promoted with phorbol ester acetate. At 1 nmol, DB[a,l]P induced 2.6 tumors/mouse, whereas DB[a,l]P-11,12-dihydrodiol and DMBA induced 0.17 and 0.29 tumors/mouse respectively. At the low dose, DB[a,l]P induced 0.79 tumors/mouse, but the other two compounds were virtually inactive. B[a]P, tested only at 1 nmol, was inactive. These three compounds, as well as DB[a,l]P-8,9-dihydrodiol, were tested by repeated application twice weekly for 40 weeks at 1 and 4 nmol per dose. In addition, DB[a,l]P, DMBA and B[a]P were also tested at 8 nmol. At 8 and 4 nmol, DB[a,l]P induced malignant tumors in 91 and 70% of mice respectively. At 4 nmol DB[a,l]P-11,12-dihydrodiol elicited only benign tumors in 36% of mice. At 4 nmol DMBA induced two carcinomas in one mouse and at 8 nmol it induced one papilloma and one sebaceous gland adenoma. B[a]P and DB[a,l]P-8,9-dihydrodiol were inactive at all doses tested. These results demonstrate that DB[a,l]P is a much more potent carcinogen than DMBA, the aromatic hydrocarbon previously considered to be the most potent. Combination of these results with previous comparisons of DB[a,l]P, DB[a,l]P-11,12-dihydrodiol, DMBA and B[a]P at higher doses (E.L. Cavalieri et al. (1991) Carcinogenesis, 12, 1939-1944) shows clearly the interference of toxicity with the tumorigenicity of DB[a,l]P and its 11,12-dihydrodiol.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias das Glândulas Sebáceas
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Neoplasias Cutâneas
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Benzo(a)pireno
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Benzopirenos
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Carcinógenos
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9,10-Dimetil-1,2-benzantraceno
Limite:
Animals
Idioma:
En
Revista:
Carcinogenesis
Ano de publicação:
1993
Tipo de documento:
Article