Comparative carcinogenicity, metabolism, mutagenicity, and DNA binding of 7H-dibenzo[c,g]carbazole and dibenz[a,j]acridine.
Complex mixtures that are produced from the combustion of organic materials have been associated with increased cancer mortality. These mixtures contain homocyclic and heterocyclic polycyclic aromatic hydrocarbons (PAHs), many of which are known carcinogens. In particular, N-heterocyclic aromatic compounds (NHA) are present in these mixtures. Studies to determine the metabolic activation of these compounds have been undertaken. The purpose of this review is to compare and contrast the metabolic activation and biological effects of two NHA, 7H-dibenzo[c,g]carbazole (DBC) and dibenz[a,j]acridine (DBA), in order to better assess the contribution of NHA to the carcinogenic potency of complex mixtures and to develop biomarkers of the carcinogenic process. DBC has both local and systemic effects in the mouse; it is a potent skin and liver carcinogen following topical application and a lung carcinogen following i.p. application. On the other hand, DBA is a moderate mouse skin carcinogen following topical application and a lung carcinogen following subcutaneous injection. The biological differences for DBC and DBA are reflected in target organ-specific proximate and mutagenic metabolites and DNA adduct patterns.
Warshawsky
D
D
Department of Environmental Health, University of Cincinnati, OH 45267-0056, USA.
Talaska
G
G
Xue
W
W
Schneider
J
J
D000166:Acridines / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D000236:Adenoma / Q000139:chemically induced; D000818:Animals; D000830:Animals, Laboratory; D002227:Carbazoles / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000378:metabolism / Q000633:toxicity*; D006224:Cricetinae; D018736:DNA Adducts / Q000378:metabolism*; D011905:Genes, ras / Q000235:genetics; D008175:Lung Neoplasms / Q000139:chemically induced; D051379:Mice; D008861:Microsomes / Q000378:metabolism; D009152:Mutagenicity Tests; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D051381:Rats; D012867:Skin / Q000378:metabolism
D000166:Acridines; D002227:Carbazoles; D002273:Carcinogens; D018736:DNA Adducts; C022289:dibenzacridine; D016283:Proto-Oncogene Proteins p21(ras); C013478:7H-dibenzo(c,g)carbazole