The carcinogenic activity of the two
polycyclic aromatic hydrocarbons (PAHs),
picene (
benzo[a]chrysene) and
dibenz[a,h]anthracene (DBA), was determined in NMRI mice by five different experimental protocols in order to find out if
picene is a
carcinogen as predicted by recent quantum mechanical calculations in contrast to earlier observations which could not confirm any carcinogenic activity of
picene. Single s.c. treatment of adult mice with
picene or DBA (308 nmol/animal, each) led to the formation of
fibrosarcomas in 63.3% of treated animals regardless of the PAH used. Chronic epicutaneous application of both PAHs (total dose 1.36 mumol) to the back of mice resulted in the development of
papillomas with a
tumor rate of 22% in the case of
picene and of 32% in the case of DBA. When newborn mice were s.c. treated once on day 2 of their life with each of the two PAHs (400 nmol/animal), 27.8% of treated animals developed lung
adenomas after 40 weeks in the case of
picene compared to 92.1% in the case of DBA. Histopathological examination of the
tumors in the three experimental models revealed no difference in the type of
tumor between
picene and DBA. Epicutaneous application of both PAHs (600 nmol/animal) followed by chronic treatment with 12-O-tetradecanoyl-phorbol-13-acetate for 24 weeks led to the formation of
papillomas in 93% of animals treated with DBA while
picene showed no tumorigenic activity at all. Initiation of
tumorigenesis in the two-stage
tumor model with 7,12-dimethylbenz[a]
anthracene (1 mumol/animal) and chronic treatment with
picene (total dose 4.8 mumol) for 24 weeks was equally ineffective in producing
tumors in NMRI mice. This rare
biological property of
picene, which is a complete
carcinogen, yet at most a very weak
tumor initiator, is explained in terms of its inefficient biotransformation to mutagenic and carcinogenic metabolites as compared to the strong
tumor initiator DBA.