Comparative mutagenicity of 7H-dibenzo[c,g]carbazole and two derivatives in Muta™Mouse liver and skin

7H-Dibenzo[c,g]carbazole (DBC) is an environmental pollutant that produces DNA adducts and tumors in mouse liver and skin following subcutaneous injection and topical application. The two synthetic derivatives 5,9-dimethyl-DBC (DMDBC) and N7-methyl-DBC (NMDBC) induce tissue-specific lesions. DNA adducts and tumors are observed only in liver following exposure to DMDBC and only in skin following exposure to NMDBC. We used the positive selection Muta(TM)Mouse model to measure the induction of mutations in the two target organs, 28 days after a single subcutaneous injection or topical application of DEC, DMDBC and NMDBC. In liver, DEC and DMDBC induced 30- to 50-fold increases in mutant frequency (MF), while NMDBC had only a weak effect, regardless of the route of administration. After topical application, DEC and NMDBC produced 3.4- to 7.9-fold increases in MF in skin, while DMDBC had a weak effect. After subcutaneous injection, the three compounds had no or weak effect in skin. This study shows gene mutations arise in the respective target organs in which primary DNA damage and tumors are observed. These results illustrate the relevance of the Muta(TM)Mouse model for testing organ-specific mutagens. (C) 1998 Elsevier Science B.V. All rights reserved.