INDUCTION OF KARYOTYPE INSTABILITY IN A MURINE TUMOR-CELL LINE BY QUERCETIN, 2-AMINO-1-METHYL-6 PHENYLIMIDAZO[4,5-B]PYRIDINE, AND OKADAIC ACID, AS REVEALED BY TRANSMISSION DISTORTION OF THE INACTIVE X-CHROMOSOME

Quercetin, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhlP), and okadaic acid are found in various foods and have been shown to have m utagenic or promoter-like activity. The effects of these three compoun ds on the transmission of the inactive X chromosome were examined in M ST-CG murine tumor cells, which were derived from hybrid F-1 mice from matings between C57BL/6 and MSM mice. Polymerase chain reaction analy sis using polymorphic markers on the X chromosome detected transmissio n distortion of the inactive X chromosome due to nondisjunction as a c opy-number imbalance in allelic bands. The cells exposed to all three chemicals (but not untreated cells) exhibited such imbalances at high frequencies under exposure conditions similar to those in previous exp eriments in which tumor progression and recombination were observed. T he cells also showed increased frequencies of tumor formation when sub cutaneously injected. These results suggest that the three chemicals a re capable of inducing transmission distortion of the inactive X chrom osome and that such activity may be a causative factor in promoting th e tumorigenicity of MST-CG cells. (C) 1995 Wiley-Liss, Inc.