Tissue-specific DNA adduct formation in mice treated with the environmental carcinogen, 7H-dibenzo[c,g]carbazole.
Covalent adduction of DNA by chemical agents is commonly thought to be an essential part of the initiation of chemical carcinogenesis. Until recently, assays of DNA damage by covalent binding of chemicals have been restricted mostly to substances that are available in radiolabeled form, which excludes many environmental compounds with carcinogenic potential. In this paper, the binding of non-radioactive 7H-dibenzo[c,g]carbazole (DBC), a known environmental carcinogen, to DNA in female CD-1 mice after s.c. injection of 44 mumol/kg of the compound has been investigated using a 32P-postlabeling assay. DBC showed strong hepatic specificity with a mean total level of 107 adducts per 10(7) nucleotides at 24 h, while much lower levels of binding were seen in kidney, lung, spleen, skin and brain with 4.3, 2.1, 1.3, 0.4 and 0.04 adducts, respectively, per 10(7) nucleotides. Proportions of individual DBC adducts also varied considerably between tissues. The degree of hepatic preference displayed by DBC is not seen with other polycyclic aromatic carcinogens such as benzo[a]pyrene and 2-acetylaminofluorene. The DNA-binding data, together with other hepatotoxic effects of the compound, may be causally related to the known hepatocarcinogenicity of DBC.
D015073:2-Acetylaminofluorene / Q000378:metabolism; D000818:Animals; D002227:Carbazoles / Q000378:metabolism*; D002274:Carcinogens, Environmental / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D005260:Female; D008099:Liver / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains
D002227:Carbazoles; D002274:Carcinogens, Environmental; D004247:DNA; D015073:2-Acetylaminofluorene; C013478:7H-dibenzo(c,g)carbazole