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
K. Kuwabara et al., 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, Molecular carcinogenesis, 14(4), 1995, pp. 299-305
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.