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Tumorigenicity studies with diol-epoxides of benzo(a)pyrene which indicate that (+-)-trans-7. beta. ,8. cap alpha. -dihydorxy-9. cap alpha. ,10. cap alpha. -epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene is an ultimate carcinogen in newborn mice

Journal Article · · Cancer Res.; (United States)
OSTI ID:6783279
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The tumorigenic activities of benzo(a)pyrene (BP), (+-)-trans-7..beta..,8..cap alpha..-dihydroxy-9..beta..,10..beta..-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (diol-epoxide 1), (+-)-trans-7..beta..,8..cap alpha..-dihydroxy-9..cap alpha..,10..cap alpha..-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (diol-epoxide 2), (+-)-trans-7,8,-dihydroxy-7,8-dihydrobenzo(a)pyrene (BP 7,8-dihydrodiol), and the tetraols derived from the hydrolysis of diol-epoxide 2 were evaluated in newborn mice. The mice were given injections sequentially of 4,8, and 16 nmoles of each compound on the first, eighth, and fifteenth days of life, and the animals were killed when they were 28 weeks old. Diol-epoxide 1 was highly toxic in newborn mice, and most of the animals treated with this compound died before weaning. Diol-epoxide 2 and BP 7,8-dihydrodiol were, respectively, about 40- and 15-fold more active than BP in causing pulmonary adenomas. Vehicle-treated control animals had an average of 0.13 lung adenoma/mouse, whereas animals treated with BP, BP 7,8-dihydrodiol, or diol-epoxide 2 had, respectively, 0.24, 1.77, and 4.42 pulmonary adenomas/mouse. Diol-epoxide 1 and the tetraols derived from diol-epoxide 2 did not induce pulmonary adenomas. The inactivity of diol-epoxide 1 under the conditions of our study should be interpreted with caution because of the high toxicity of this compound. The results of our study provide evidence that BP 7,8-dihydrodiol is a proximate carcinogenic metabolite and that diol-epoxide 2 is an ultimate carcinogenic metabolite of BP in the newborn mouse.

Research Organization:
Hoffmann-La Roche Inc., Nutley, NJ
OSTI ID:
6783279
Journal Information:
Cancer Res.; (United States), Journal Name: Cancer Res.; (United States) Vol. 38:2; ISSN CNREA
Country of Publication:
United States
Language:
English

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Related Subjects

560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADENOMAS
ALCOHOLS
ANIMAL CELLS
ANIMALS
AROMATICS
BENZOPYRENE
BIOLOGICAL EFFECTS
BODY
CARCINOGENS
CHEMICAL ACTIVATION
CONDENSED AROMATICS
DISEASES
GLYCOLS
HYDROCARBONS
HYDROXY COMPOUNDS
LUNGS
MAMMALS
METABOLITES
MICE
NEONATES
NEOPLASMS
ORGANIC COMPOUNDS
ORGANS
RESPIRATORY SYSTEM
RODENTS
TUMOR CELLS
VERTEBRATES