TUMOR-INITIATING ACTIVITY ON MOUSE SKIN OF BAY-REGION DIOL-EPOXIDES OF 5,6-DIMETHYLCHRYSENE AND BENZO[C]PHENANTHRENE

Citation
S. Amin et al., TUMOR-INITIATING ACTIVITY ON MOUSE SKIN OF BAY-REGION DIOL-EPOXIDES OF 5,6-DIMETHYLCHRYSENE AND BENZO[C]PHENANTHRENE, Carcinogenesis, 14(10), 1993, pp. 2033-2037
Citations number
35
Categorie Soggetti
Oncology
Journal title
ISSN journal
01433334
Volume
14
Issue
10
Year of publication
1993
Pages
2033 - 2037
Database
ISI
SICI code
0143-3334(1993)14:10<2033:TAOMSO>2.0.ZU;2-Y
Abstract
Previous metabolism and DNA-binding studies indicated that 5,6-dimethy lchrysene (5,6-diMeC) is metabolically activated in mouse skin through formation of its 1,2-dihydrodiol (5,6-diMeC-1,2-diol) and bay region diol-epoxide (anti-5,6-diMeC-1,2-diol-3,4-epoxide). These metabolites were tested as tumor initiators on mouse skin. Included for comparison were syn-5,6-diMeC-1,2-diol-3,4-epoxide and y-2,1-epoxy-4,3,2,1-tetra hydrobenzo[c]phenanthrene (anti-B[c]Ph-4,3-diol-2,1-epoxide). At an in itiating dose of 100 nmol/mouse, 5,6-diMeC-1,2-diol and anti-5,6-diMeC -1,2-diol-3,4-epoxide were significantly more tumorigenic than 5,6-diM eC, inducing 7.1 and 3.9 skin tumors per mouse respectively compared t o 1.1 induced by 5,6-diMeC. Similar results were obtained at an initia ting dose of 33 nmol/mouse. This is the first example of a methylated polynuclear aromatic hydrocarbon bay region diol-epoxide which is more tumorigenic than its parent hydrocarbon on mouse skin. syn-5,6-diMeC- 1,2-diol-3,4-epoxide was only weakly tumorigenic. Comparisons of anti- 5,6-diMeC-1,2-diol-3,4-epoxide and anti-B[c]Ph-4,3-diol-2,1-epoxide de monstrated that the latter was a stronger tumor initiator. The results of this study confirm the bay region diol-epoxide metabolic activatio n pathway of 5,6-diMeC but do not provide an explanation for the relat ively weak tumorigenicity of this hydrocarbon on mouse skin.