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. Exp Lung Res 2001;27(3):245-53
Date
04/11/2001Pubmed ID
11293327DOI
10.1080/019021401300054000Scopus ID
2-s2.0-0035076969 (requires institutional sign-in at Scopus site) 18 CitationsAbstract
Polycyclic aromatic hydrocarbons (PAH) and N-heterocyclic aromatic hydrocarbons (NHA) are environmental pollutants formed during the incomplete combustion of organic materials. Benzo(a)pyrene (BaP) and 7H-dibenzo(c,g)carbazole (DBC) are well-characterized representatives of the PAH and NHA classes of compunds, respectively. Both are demonstrated carcinogens that frequently co-occur in environmental mixtures. This preliminary study was conducted to investigate the effects of a binary mixture of BaP and DBC on lung carcinogenicity in the strain A/J mouse as manifested by tumor development and mutations in the K-ras gene. Male A/J mice were administered the following single 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. Mice were sacrificed 8 months after carcinogen treatment and lung tumor multiplicity and K-ras mutations determined (high-dose combination). The combination of DBC and BaP produced fewer tumors than the sum of all tumors produced by each compound acting alone. The frequency of tumors with K-ras mutations 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 produced by BaP and DBC were expressed in tumors from animals treated with the mixture.
Author List
Gray DL, Warshawsky D, Xue W, Nines R, Wang Y, Yao R, Stoner GDMESH terms used to index this publication - Major topics in bold
AnimalsBenzo(a)pyrene
Carbazoles
Carcinogens
Environmental Pollutants
Genes, ras
Lung Neoplasms
Male
Mice
Mice, Inbred A
Mutation
