Hepatocarcinogen quinoline induces G : C to C : G transversions in the cIIgene in the liver of lambda/lacZ transgenic mice (Muta (TM) Mouse)

Quinoline is carcinogenic to the liver in rodents, but it is not clear whet her it acts by a genotoxic mechanism. We previously demonstrated that quino line does induce gene mutation in the liver of lambda/lacZ transgenic mice. In the present report, we reveal the molecular nature of the mutations ind uced by quinoline in the lambda cII gene, which is also a phenotypically se lectable marker in the lambda transgene. (The cII gene has 294 bp, which en ables much easier sequence analysis than the original lacZ gene (3 kb)). Th e liver cII mutant frequency was nine times higher in quinoline-treated mic e than in control mice. Sequence analysis revealed that quinoline induced p rimarily G:C to C:G transversions (25 of 34). Thus, we have confirmed that quinoline is genotoxic in its target organ, and the G:C to C:G transversion is the molecular signature of quinoline-induced mutations. (C) 2000 Elsevi er Science B.V. All rights reserved.