Reduction of tumorigenicity and of dihydrodiol formation by fluorine substitution in the angular rings of dibenzo(a,i)pyrene
Hecht, SS; Lavoie, EJ; Bedenko, V; Pingaro, L; Katayama, S; Hoffmann, D; Sardella, DJ; Boger, E; Lehr, RE
HERO ID
1406635
Reference Type
Journal Article
Year
1981
Language
English
PMID
| HERO ID | 1406635 |
|---|---|
| In Press | No |
| Year | 1981 |
| Title | Reduction of tumorigenicity and of dihydrodiol formation by fluorine substitution in the angular rings of dibenzo(a,i)pyrene |
| Authors | Hecht, SS; Lavoie, EJ; Bedenko, V; Pingaro, L; Katayama, S; Hoffmann, D; Sardella, DJ; Boger, E; Lehr, RE |
| Journal | Cancer Research |
| Volume | 41 |
| Issue | 11 Pt 1 |
| Page Numbers | 4341-4345 |
| Abstract | The tumor-initiating activities on mouse skin and in vitro metabolism of dibenzo(a,i)pyrene, 2-fluorodibenzo(a,i)pyrene, 3-fluorodibenzo(a,i)pyrene, and 2, 10-difluorodibenzo(a,i)pyrene were compared. After an initiating dose of 500 micrograms, followed by promotion with tetradecanoylphorbol acetate, dibenzo(a,i)pyrene induced skin tumors in 85% of the mice and caused 5.8 skin tumors/mouse. The corresponding tumorigenic activities for the fluorinated compounds were: 2-fluorodibenzo(a,i)pyrene (85%; 1.7 tumors/mouse); 3-fluorodibenzo(a,i)pyrene (80%; 3.1 tumors/mouse); and 2,10-difluorodibenzo(a,i)pyrene (10%; 0.1 tumors/mouse). After an initiating dose of 100 micrograms, only dibenzo(a,i)pyrene showed significant tumor-initiating activity. 3,4-Dihydro-3,4-dihydroxydibenzo(a,i)pyrene was identified as a metabolite of dibenzo(a,i)pyrene formed by the 9000 X g supernatant from the livers of Aroclor 1254-pretreated rats. Another dihydrodiol was tentatively identified as 1,2-dihydro-1,2-dihydroxydibenzo(a,i)pyrene. The formation of these angular ring dihdrodiols was inhibited in the metabolism of 2-fluorodibenzo(a,i)pyrene and 3-fluorodibenzo(a,i)pyrene. Angular ring dihydrodiols were not detected in the metabolism of 2,10-difluorodibenzo(a,i)pyrene. These results suggest that an angular ring dihydrodiol, 3,4-dihydro-3,4-dihydroxydibenzo(a,i)pyrene, which can form a bay-region dihydrodiol epoxide, may be a proximate carcinogen of dibenzo(a,i)pyrene. |
| Pmid | 7306963 |
| Wosid | WOS:A1981MN48300021 |
| Url | http://cancerres.aacrjournals.org/content/41/11_Part_1/4341.abstract |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |
| Relationship(s) |
|