7H-BENZO[C]FLUORENE: A POTENT SYSTEMIC LUNG CARCINOGEN

Abstract

7H-Benzo[c]fluorene (B[c]F) is a major lung deoxyribonucleic acid (DNA) adductor in mice treated with coal tar suggesting that B[c]F may be capable of inducing lung tumors. This study evaluated the tumorigenic potential of B[c]F in comparison to benzo[a]pyrene (B[a]P) using the A/J mouse model. Female A/J mice 7 weeks of age were administered B[c]F or B[a]P (100 mg/kg) by i.p. injection. These mice were fed Purina Rodent 2001 diet for the remainder of the study. Groups of mice were also fed diets containing B[c]F (397 or 27 μmol/kg diet) or B[a]P (397 μmol/kg diet). In addition, a mixture of 20 synthetic polycyclic aromatic hydrocarbons (PAHs) known to be present in coal tar was also fed to mice in the presence or absence of B[c]F. A basal gel diet system was used to administer hydrocarbons within the diet. Mice were maintained on control or adulterated diets for 260 days. B[c]F administered i.p. induced multiple lung tumors in 92% of the treated mice, with an average of 4.0 tumors per mouse. Similarly, B[a]P administered i.p. induced an average of 6.7 tumors per mouse in 90% of the treated mice. The highest level of lung tumor induction was observed in mice fed 397 μmol/kg diet B[c]F. A 100% tumor incidence and an average of 46 lung tumors per mouse was observed. In contrast, mice fed a diet containing 397 μmol/kg of B[a]P, had a 77% tumor incidence with an average of 1.4 tumors per mouse. Mice fed a 27 μmol/kg B[c]F diet, or the mixture of synthetic hydrocarbons with or without B[c]F resulted in tumor incidences and multiplicity not different from controls. Forestomach lesions were greatest in mice treated with B[a]P. Evaluation of chemical:DNA adduct formation in mice indicates that B[c]F is better than B[a]P in forming lung DNA adducts when fed to mice at 397 μmol/kg food. These results demonstrate that B[c]F is tumorigenic in lung of mice when administered by i.p. injection and in particular when fed to mice in the diet. These data strongly suggest that B[c]F is a systemic carcinogen that likely contributes to the potent mouse lung tumorigenicity previously demonstrated with coal tar when fed to mice.