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 (PhIP), and okadaic acid are found in various foods and have been shown to have mutagenic or promoter-like activity. The effects of these three compounds on the transmission of the inactive X chromosome were examined in MST-C6 murine tumor cells, which were derived from hybrid F1 mice from matings between C57BL/6 and MSM mice. Polymerase chain reaction analysis using polymorphic markers on the X chromosome detected transmission distortion of the inactive X chromosome due to nondisjunction as a copy-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 experiments in which tumor progression and recombination were observed. The cells also showed increased frequencies of tumor formation when subcutaneously injected. These results suggest that the three chemicals are capable of inducing transmission distortion of the inactive X chromosome and that such activity may be a causative factor in promoting the tumorigenicity of MST-C6 cells.
Kuwabara
K
K
First Department of Biochemistry, Faculty of Education, Niigata University, Japan.
Odani
S
S
Takahashi
Y
Y
Arakawa
M
M
Takagi
N
N
Nagao
M
M
Kominami
R
R
D000818:Animals; D015139:Blotting, Southern; D002273:Carcinogens / Q000633:toxicity*; D004273:DNA, Neoplasm / Q000187:drug effects / Q000235:genetics; D004303:Dosage Compensation, Genetic; D004988:Ethers, Cyclic / Q000633:toxicity*; D005260:Female; D005354:Fibrosarcoma / Q000235:genetics*; D007093:Imidazoles / Q000633:toxicity*; D007621:Karyotyping; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009153:Mutagens / Q000633:toxicity*; D019319:Okadaic Acid; D011110:Polymorphism, Genetic; D011794:Quercetin / Q000633:toxicity*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014960:X Chromosome / Q000187:drug effects*
D002273:Carcinogens; D004273:DNA, Neoplasm; D004988:Ethers, Cyclic; D007093:Imidazoles; D009153:Mutagens; D019319:Okadaic Acid; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; D011794:Quercetin