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

D. L. Gray, D. Warshawsky, W. Xue, R. Nines, Y. Wang, R. Yao, G. D. Stoner

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

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 compounds, 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.

Original languageEnglish (US)
Pages (from-to)245-253
Number of pages9
JournalExperimental Lung Research
Volume27
Issue number3
DOIs
StatePublished - 2001

Keywords

  • K-ras
  • Lung tumors
  • Polycyclic aromatic hydrocarbons (PAHs)
  • Strain A/J mouse

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry

Fingerprint

Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this