Identification of tumor promotion marker genes for predicting tumor promoting potential of chemicals in BALB/c 3T3 cells.
Tumor promoters can cause development of tumors in initiated cells and the majority of them are non-genotoxic carcinogens. The detection of tumor promoters is important for the prevention of cancer. The in vitro two-stage transformation assay, using BALB/c 3T3 cells, is a useful system, and benefits from a convenient protocol and high predictability of mammalian carcinogenicity. But these assays are time-consuming and often require expertise for microscopic observation. To construct an in vitro tumor promoting activity test system, we performed large-scale gene expression analyses, using DNA microarrays, of BALB/c 3T3 cells following treatment with nine chemicals that are known to induce tumor promotion: TPA, zinc chloride, sodium orthovanadate, okadaic acid, insulin, lithocolic acid, phenobarbital sodium, sodium saccharide, sodium arsenite. As a result of DNA microarray and real time PCR analyses, 22 marker genes were identified. These consisted of genes related to cell cycle, regulation of transcription, anti-apoptosis, and positive regulation of cell proliferation. There was a correlation between these 22 marker genes and the cell transformation assay results in BALB/c 3T3 cells. These results suggest that this tumor promoting activity test system, based on 22 marker genes, can become a valuable tool for screening potential tumor promoters.
Maeshima
Hideki
H
Food Safety Research Institute, Nissin Food Products Co., Ltd., 2247, Noji-Cho, Kusatsu, Shiga 525-0055, Japan. h-maeshima@mb1.nissinfoods.co.jp
Ohno
Katsutoshi
K
Tanaka-Azuma
Yukimasa
Y
Nakano
Shigeru
S
Yamada
Toshihiro
T
D000818:Animals; D041702:BALB 3T3 Cells / Q000187:drug effects* / Q000378:metabolism; D015197:Carcinogenicity Tests / Q000379:methods; D002273:Carcinogens / Q000145:classification / Q000633:toxicity*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005819:Genetic Markers; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000378:metabolism; D015262:Xenobiotics / Q000145:classification / Q000633:toxicity*
D002273:Carcinogens; D005819:Genetic Markers; D012333:RNA, Messenger; D015262:Xenobiotics