| Autor: |
Koganti, Aruna, Singh, Renu, Rozett, Kimberly, Modi, Nehal, Goldstein, Lawrence S., Roy, Tim A., Zhang, Fang Jie, Harvey, Ronald G., Weyand, Eric H. |
| Zdroj: |
Carcinogenesis; Aug2000, Vol. 21 Issue 8, p1601-1609, 9p |
| Abstrakt: |
Coal tar is a complex mixture that exhibits high carcinogenic potency in lungs of animals when administered in the diet. Studies have noted that lung tumor induction does not correlate with the benzo[a]pyrene content of coal tar, suggesting that other hydrocarbons may be involved in the observed tumorigenicity. Our previous studies have demonstrated that a major `unknown' chemical–DNA adduct is formed in the lung of mice exposed to coal tar. We have used an in vitro rat microsomal activation system to generate the `unknown' adduct with neat coal tar and fractions of coal tar obtained by chemical fractionation and HPLC. Chemical–DNA adduct formation was evaluated by 32P-postlabeling using both multi-dimensional TLC and HPLC. GC–MS analysis of the coal tar fractions obtained from HPLC, which produced the `unknown' adduct in vitro, demonstrated that the adducting hydrocarbon had a mass of 216. A careful evaluation of candidate hydrocarbons led to the conclusion that a benzofluorene derivative may be responsible for forming the `unknown' chemical–DNA adduct. Comparative in vitro and in vivo studies on the adducting properties of all three isomers of benzofluorene indicated that 7H-benzo[c]fluorene is responsible for producing the `unknown' adduct observed in the lung of mice ingesting coal tar. Animal feeding studies also demonstrated that 7H-benzo[c]fluorene formed considerably more lung DNA adducts than 11H-benzo[a]fluorene and 11H-benzo[b]fluorene. These data indicate that the four-ring polycyclic aromatic hydrocarbon 7H-benzo[c]fluorene, a hydrocarbon not previously shown to form DNA adducts in lung, is in fact a potent lung DNA adductor and is a candidate PAH for causing lung tumors in animals treated with coal tar. [ABSTRACT FROM PUBLISHER] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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