title: Induction of minisatellite mutation in NIH 3T3 cells by treatment with the tumor promoter okadaic acid.
abstract: Okadaic acid (OA) is a strong tumor promoter of mouse skin carcinogenesis and also a potent inhibitor of serine/threonine protein phosphatases. OA induces various genetic alterations in cultured cells, such as diphtheria-toxin-resistance mutations, sister chromatid exchange, exclusion of exogenous transforming oncogenes, and gene amplification. The present study revealed that it caused minisatellite mutation (MSM) at a high frequency in NIH 3T3 cells, although no microsatellite mutation was found. Nine of 31 clones (29%) exhibited MSM after 6 days of OA treatment, as opposed to only 1 of 30 clones (3%) without OA exposure. Moreover, NIH 3T3 cells treated with OA acquired tumorigenicity in nude mice, giving rise to 7 tumors within 25 weeks in 20 sites where 3 x 10(6) cells were injected. In contrast, the same numbers of untreated cells gave rise to only one tumor, and the tumor grew much slower. All of three OA-induced tumors examined manifested the MSM. The findings thus point to a molecular mechanism by which OA could function as a tumor promoter, and also the biological relevance of the induction of MSM in the tumorigenic process by OA.
authors.affiliation: Biochemistry, National Cancer Center Research Institute, 1-1, Tsukiji 5, Chuo-ku, Tokyo 104, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nakagama
authors.forename: S
authors.initials: S
authors.lastname: Kaneko
authors.forename: H
authors.initials: H
authors.lastname: Shima
authors.forename: H
authors.initials: H
authors.lastname: Inamori
authors.forename: H
authors.initials: H
authors.lastname: Fukuda
authors.forename: R
authors.initials: R
authors.lastname: Kominami
authors.forename: T
authors.initials: T
authors.lastname: Sugimura
authors.forename: M
authors.initials: M
authors.lastname: Nagao
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D003001:Cloning, Molecular; D016172:DNA Fingerprinting; D004260:DNA Repair; D004276:DNA, Satellite / Q000187:drug effects* / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D009153:Mutagens / Q000494:pharmacology*; D019319:Okadaic Acid / Q000494:pharmacology*; D019680:Trinucleotide Repeat Expansion; D014407:Tumor Cells, Cultured
chemical_list: D002273:Carcinogens; D004276:DNA, Satellite; D009153:Mutagens; D019319:Okadaic Acid