Reference SummaryGray DL, Exp Lung Res 2001 Apr-May;27(3):245-53

Title

 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.

Authors

 Gray DL; Warshawsky D; Xue W; Nines R; Wang Y; Yao R; Stoner GD

Journal

 Exp Lung Res

Volume

 27

Issue

 3

Year

 2001

Pages

 245-53

Abstract

 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.

Links

 J:68460 – MGI References
11293327 – National Library of Medicine/PubMed

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
A/J Lung tumor
  • 7H-dibenzo[c,g]carbazole (3,4,5,6-dibenzocarbazole) (DBC)
 Lung

89 - 100
A/J Lung tumor
  • benzo[a]pyrene (BP) (BaP) (B[a]P)
 Lung

29 - 100
A/J Lung tumor
  • benzo[a]pyrene (BP) (BaP) (B[a]P)
  • 7H-dibenzo[c,g]carbazole (3,4,5,6-dibenzocarbazole) (DBC)
 Lung

33 - 100
A/J Lung tumor Lung

17