The production of cancer by pure hydrocarbons.--Part III
Authors: Barry, G; Cook, JW; Haslewood, GAD; Hewett, CL; Hieger, I; Kennaway, EL
Proceedings of the Royal Society: Biological Sciences 117:318-351.
HERO ID: 1012335
The carcinogenic activity of tetracyclic and pentacyclic aromatic hydrocarbons was investigated. Substances . . .
The carcinogenic activity of tetracyclic and pentacyclic aromatic hydrocarbons was investigated. Substances were applied in benzene solution to the interscapular region of mice twice weekly. Tests for the production of sarcoma were made by injecting the compound subcutaneously in a fatty medium, generally lard. Tetracyclic compounds including 3,4-benzpyrene (50328) (34BP) and 3,4-benzphenanthrene (217594) (34BPA), 20 simple homologues of 1,2-benzanthracene (56553) (12BA), 12 pentacyclic compounds including 1,2,5,6-dibenzanthracene (53703) (1256DB), 1,2-benzpyrene (192972), 20 simple derivatives of 1256DB, methylcholanthrene (56495), certain sterols and their derivatives, keto hydroxyoestrin (53167) and some derivatives, and allied compounds were tested. In all, 71 compounds not related in molecular structure to 12BA and 69 compounds related to 12BA were tested. Of those not related to 12BA, 34BPA, pyrene (129000), chrysene (218019), and their derivatives produced tumors. The most active of these, 34BPA, produced 7 epitheliomas and 5 papillomas in 20 mice tested. Of the 69 compounds related to 12BA, 25 were carcinogenic. In general, these active compounds were all derivatives of 12BA containing substituents at positions five or six or both, these substituents being alkyl groups, saturated rings, or an additional aromatic ring. Active compounds related to 12BA but not within these categories were 1,2-benzpyrene, 1,2,7,8-dibenzanthracene (224419), and its analogue 3,4,5,6-dibenzacridine (224533). Methylcholanthrene (56495), a benzanthracene hydrocarbon with substituents in positions five and six, was a potent carcinogen: in one series of 20 mice, 17 epitheliomas and 1 papilloma were produced in 180 days. The 44 compounds related to 12BA which were not carcinogenic were usually derivatives in which the substituents were attached to the molecule at positions other than five and six, or else compounds related to 1256DB by the attachment of additional benzene. The authors suggest that there is an optimum state of molecular complexity for carcinogenic activity.