7 H -benzo[ c ]fluorene: a major DNA adduct-forming component of coal tar

Abstract

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 (32)P-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.

Comparative potency approach based on H2AX assay for estimating the genotoxicity of polycyclic aromatic hydrocarbons

“…BcF was found to be nonmutagenic in the Ames assay (Lavoie et al, 1981) but was able to form DNA adducts in vivo (Koganti et al, 2000;Weyand et al, 2002;Cizmas et al, 2004). In addition, it is considered as a more potent carcinogenic hydrocarbon than BaP in rodents (Weyand et al, 2004).…”

Characterization of a major aromatic DNA adduct detected in human breast tissues

“…Mammary gland and liver tissues were removed and kept at Ϫ80°C until DNA isolation. Female CD-1 mice were fed basal gel diet containing 7H-benzo[c]fluorene (B[c]F; 60 mg/kg) ad libitum for 14 days [Koganti et al, 2000]. Mice were euthanized and lungs quickly removed and stored at Ϫ20°C before DNA isolation.…”

Benzo[c]fluorene in Urban Air: HPLC Determination and Mutagenic Contribution Relative to Benzo[a]pyrene

“…1) is still in Group 3 with respect to its carcinogenicity (not classifiable as to its carcinogenicity to humans), BcFE is genotoxic. [14][15][16][17] The United States Environmental Protection Agency (EPA) reported that the relative potency factors (RPFs) of BcFE, BjAC, and dibenz[a,h]anthracene (DBA) with respect to the mutagenicity of BaP (which has a value of 1) are 20, 60, and 10, respectively. 18 The RPFs provide a measure of the mutagenicity of a given PAH relative to that of BaP.…”