N-methylation reduces the DNA-binding activity of 7H-dibenzo[c,g]carbazole approximately 300-fold in mouse liver but only approximately 2-fold in skin: possible correlation with carcinogenic activity.
Schurdak-ME; Stong-DB; Warshawsky-D; Randerath-K
Carcinogenesis 1987 Oct; 8(10):1405-1410
The hypothesis that N-methyl-dibenzo(c,g)carbazole (27093625) (MeDBC) binds covalently to skin and thus is a topical carcinogen, was tested by using a phosphorus-32 postlabeling technique to compare the in-vivo DNA binding of MeDBC and 7H- dibenzo(c,g)carbazole (194592) (DBC) in mouse liver and skin. Female CD-1-mice were treated topically or intraperitoneally with 37 micromoles/kilogram of MeDBC or DBC. DNA adduct patterns produced by MeDBC and DBC in liver after topical or intraperitoneal administration of a dose were qualitatively similar for the two compounds. Large quantitative differences in DNA fingerprint maps were observed. Four adducts were observed in the skin after topical application of MeDBC. In skin, topical application of DBC produced six adducts. The adduct pattern elicited by either MeDBC or DBC in the liver was different from the pattern in the skin. Total adduction in skin by DBC was 2.3 fold higher than by MeDBC. Topically applied MeDBC bound preferentially to skin versus liver DNA by a factor of ten. The authors conclude that data are in agreement with the carcinogenicity reported for DBC and MeDBC and that an unsubstituted nitrogen is essential for the genotoxic activity of DBC in liver but not skin.
NIOSH-Publication; NIOSH-Grant; Carcinogenesis; Laboratory-animals; Carbazoles; Liver-cancer; Skin-cancer; Qualitative-analysis; Quantitative-analysis; In-vivo-studies
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