The effects of a binary mixture of benzo(a)pyrene and 7H-dibenzo(c,g)carbazole on lung tumors and K-ras oncogene mutations in strain A/J mice

Polycyclic aromatic hydrocarbons (PAH) and N-heterocyclic aromatic hydrocar bons (NHA) are environmental pollutants formed during the incomplete combus tion of organic materials. Benzo(a)Pyrene (BaP) and 7H-dibenzo(c,g)carbazol e (DBC) are well-characterized representatives of the PAH and NHA classes o f compounds, respectively. Both are demonstrated carcinogens that frequentl y co-occur in environmental mixtures. This preliminary study was conducted to investigate the effects of a binary mixture of BaP and DBC on lung carci nogenicity in the strain A/J mouse as manifested by tumor development and m utations it the K-ras gene. Male A/J mice were administered the following s ingle intraperitoneal dose (mg/kg) combinations of BaP and DBC dissolved in a 0.2-mL volume of tricaprylin-10 DBC:10 BaP; 2 DBC:10 BaP; 2 DBC:100 BaP; and 10 DBC: 100 BaP, and each of the compounds alone at the same doses. Mi ce were sacrificed 8 months after carcinogen treatment and lung tumor multi plicity and K-ras mutations determined thigh-dose combination). The combina tion of DBC and BaP produced fewer tumors than the sum of all tumors produc ed by each compound acting alone. The frequency of tumors with K-ras mutati ons was also less in a sample of the 10 DBC:100 BaP treatment group than in the same-dose, single compound-treated animals. The dominant mutations pro duced by BaP and DBC were expressed in tumors from animals treated with the mixture.