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 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.
Gray
D L
DL
Ohio State University, College of Medicine and Public Health, Division of Environmental Health Sciences, 1148 Arthur James Cancer Hospital, Columbus, OH 43210, USA. gray.@osu.edu
Warshawsky
D
D
Xue
W
W
Nines
R
R
Wang
Y
Y
Yao
R
R
Stoner
G D
GD
D000818:Animals; D001564:Benzo(a)pyrene / Q000008:administration & dosage / Q000633:toxicity*; D002227:Carbazoles / Q000008:administration & dosage / Q000633:toxicity*; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000633:toxicity; D011905:Genes, ras / Q000187:drug effects*; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000235:genetics*; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D009154:Mutation
D002227:Carbazoles; D002273:Carcinogens; D004785:Environmental Pollutants; D001564:Benzo(a)pyrene; C013478:7H-dibenzo(c,g)carbazole