High carcinogenicity of 2-hydroxybenzo(a)pyrene on mouse skin.

SUMMARY Benzo(a)pyrene and five isomenic phenols of benzo (a)pynene were tested for carcinogenicity by the topical application of 0.4 @moIe of each compound to the backs of C57BL/6J mice once every 2 weeks for 60 weeks. 1-, 3-, and 12-hydroxybenzo(a)pyrene were noncarcinogenic , 11-hy droxybenzo(a)pyrene was weakly carcinogenic, and 2-hy droxybenzo(a)pyrene and benzo(a)pyrene were highly car cinogenic. All of the mice treated with benzo(a)pynene or 2-hydmoxybenzo(a)pyrene had tumors after 53 weeks of treat menl, whereas only 13% of the mice treated with 11-hydnox ybenzo(a)pyrene had tumors after 60 weeks of treatment. The time required for 50% of the animals to develop tumors was 39 to 41 weeks for both benzo(a)pyrene and 2-hydnoxy benzo(a)pyrene. Most of the tumors observed were squa mous cell carcinomas. Since 4-, 5-, 6-, 7-, 8-, 9-, and 10-hydnoxybenzo(a)pynene were previously shown to be non carcinogenic on mouse skin, our present results indicate that, among the 12 possible isomemic phenols of benzo(a)pyrene, only 2-hydroxybenzo(a)pyrene is a strong carcinogen and 11-hydnoxybenzo(a)pymene is weakly active. 2-Hydroxybenzo(a)pynene is the first example of a phenolic derivative of a polycyclic aromatic hydrocarbon that pos sesses strong carcinogenic activity. Application of benzo(a)pyrene 11,12-oxide (a K-region oxide) to mouse skin under the same conditions as described above did not cause tumors. Previous studies have shown that benzo(a)pyrene 4,5-oxide (a K-region oxide) was weakly carcinogenic, benzo(a)pyrene 7,8-oxide was moderately carcinogenic, and benzo(a)pynene 9,10-oxide was inactive.