US EPA

94588 

Journal Article 

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

Wislocki, PG; Chang, RL; Wood, AW; Levin, W; Yagi, H; Hernandez, O; Mah, HD; Dansette, PM; Jerina, DM; Conney, AH 

1977 

Yes 

Cancer Research
ISSN: 0008-5472
EISSN: 1538-7445 

37 

8 

2608-2611 

English 

872089 

WOS:A1977DP66300022 

Benzo(a)pyrene and five isomeric phenols of benzo(a)pyrene were tested for carcinogenicity by the topical application of 0.4 Ámole 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-hydroxybenzo(a)pyrene was weakly carcinogenic, and 2-hydroxybenzo(a)pyrene and benzo(a)pyrene were highly carcinogenic. All of the mice treated with benzo(a)pyrene or 2-hydroxybenzo(a)pyrene had tumors after 53 weeks of treatment, whereas only 13% of the mice treated with 11-hydroxybenzo(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-hydroxybenzo(a)pyrene. Most of the tumors observed were squamous cell carcinomas. Since 4-, 5-, 6-, 7-, 8-, 9-, and 10-hydroxybenzo(a)pyrene were previously shown to be noncarcinogenic on mouse skin, our present results indicate that, among the 12 possible isomeric phenols of benzo(a)pyrene, only 2-hydroxybenzo(a)pyrene is a strong carcinogen and 11-hydroxybenzo(a)pyrene is a strong carcinogen and 11-hydroxybenzo(a)pyrene is weakly active. 2-Hydroxybenzo(a)pyrene is the first example of a phenolic derivative of a polycyclic aromatic hydrocarbon that possesses 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)pyrene 9,10-oxide was inactive.