Carcinogenicity of 7H-dibenzo[c,g]carbazole, dibenz[a,j]acridine and benzo[a]pyrene in mouse skin and liver following topical application.
N-Heterocyclic aromatics are by-products of incomplete combustion of organic material. The overall objective of this study was to determine the relative carcinogenic potencies of 7H-dibenzo[c,g]carbazole (DBC) and dibenz[a,j]acridine (DBA) in a bioassay of complete carcinogenicity on mouse skin in a sensitive strain (Hsd:ICR(Br)) which has been used in metabolism and DNA binding studies of N-heterocyclic aromatics. No-treatment, acetone and benzo[a]pyrene (BaP)-treated animals were used as negative and positive control groups. DBC (50 nmol), DBA (50 nmol), BaP (50 nmol) or DBC plus BaP (25 nmol + 25 nmol) were applied twice weekly in 50 microliters acetone to the backs of 50 female mice/group for 99 weeks or until the appearance of a tumor. DBC, DBA, BaP and DBC plus BaP produced skin tumors in 43, 32, 49 and 42 of 50 mice each based on weekly visual observations with latent periods of 55.1, 62.2, 33.4 and 33.8 weeks, respectively. The histopathology data indicated primary skin lesions in 42, 27, 48 and 47 mice for DBC, DBA, BaP and DBC plus BaP, respectively. In addition, primary liver lesions in 37 mice were present in the DBC group. The morphological and morphometric data indicated a significant increase (P < or = 0.05) in mononuclear cells in the dermis for the BaP and DBC plus BaP groups relative to the control group. Significant increases (P < or = 0.05) were observed in the nuclear area, nucleoli per nucleus and cellular area of hepatocytes in the DBC treatment group relative to the control group. These data indicate that DBC is a potent liver carcinogen as well as a skin carcinogen following topical application.
Department of Environmental Health, University of Cincinnati, College of Medicine, OH 45267-0056.
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D
Warshawsky
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Barkley
M L
ML
Miller
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K
LaDow
A
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Andringa
D000166:Acridines / Q000008:administration & dosage / Q000633:toxicity*; D000287:Administration, Topical; D000818:Animals; D001564:Benzo(a)pyrene / Q000008:administration & dosage / Q000633:toxicity*; D002227:Carbazoles / Q000008:administration & dosage / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D018736:DNA Adducts / Q000378:metabolism; D005260:Female; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced*; D008175:Lung Neoplasms / Q000139:chemically induced; D051379:Mice; D008813:Mice, Inbred ICR; D012878:Skin Neoplasms / Q000139:chemically induced*
D000166:Acridines; D002227:Carbazoles; D002273:Carcinogens; D018736:DNA Adducts; C022289:dibenzacridine; D001564:Benzo(a)pyrene; C013478:7H-dibenzo(c,g)carbazole