Tsang S S, Stich H F
Environmental Carcinogenesis Unit, British Columbia Cancer Research Centre, Vancouver, Canada.
Cancer Lett. 1988 Dec 1;43(1-2):93-8. doi: 10.1016/0304-3835(88)90219-4.
Cultured C3H/10T1/2 cells transfected with the plasmid pdBPV-1 were used as targets, and the frequency of transformed colonies as the endpoint to test the enhancing capacity of four promoters: 12-O-tetradecanoylphorbol-13-acetate (TPA), 4-O-methyl-tetradecanoylphorbol-13-acetate (4-O-methyl-TPA), mezerein and phorbol-12-retinoate-13-acetate (PRA). The frequency of the transfected C3H/10T1/2 cells to form transformed colonies was enhanced in the following order: mezerein greater than PRA greater than TPA greater than 4-O-methyl-TPA. The amount of promoters required to promote a tenfold increase in transformed cells was 0.24, 0.81, 30 and 100 ng/ml mezerein, PRA, TPA and 4-O-methyl-TPA, respectively. A significant promoting effect was obtained by a 3.5-day exposure to mezerein regardless of whether it was added at different time intervals after transfection with BPV-DNA. The examined promoters lacked genotoxic activity, as tested on Chinese hamster ovary cells, using chromatid aberrations and exchanges, frequency of macronuclei, unscheduled DNA synthesis (UDS) and inhibition of UDS as endpoints. The usefulness of BPV-1-induced transformation as a bioassay for detecting chemicals with promoting activities is discussed.
将用质粒pdBPV-1转染的C3H/10T1/2培养细胞用作靶细胞，并以转化菌落的频率作为检测四种启动子增强能力的终点：12-O-十四烷酰佛波醇-13-乙酸酯（TPA）、4-O-甲基-十四烷酰佛波醇-13-乙酸酯（4-O-甲基-TPA）、大戟二萜醇酯和佛波醇-12-视黄酸-13-乙酸酯（PRA）。转染的C3H/10T1/2细胞形成转化菌落的频率按以下顺序增强：大戟二萜醇酯＞PRA＞TPA＞4-O-甲基-TPA。促进转化细胞增加10倍所需的启动子量分别为：大戟二萜醇酯0.24 ng/ml、PRA 0.81 ng/ml、TPA 30 ng/ml和4-O-甲基-TPA 100 ng/ml。无论在转染BPV-DNA后不同时间间隔添加大戟二萜醇酯，经3.5天暴露均可获得显著的促进作用。在所检测的启动子中，以中国仓鼠卵巢细胞为实验对象，采用染色单体畸变与交换、微核频率、非程序DNA合成（UDS）及UDS抑制作为终点指标，均未检测到遗传毒性活性。文中讨论了BPV-1诱导转化作为检测具有促进活性化学物质的生物测定方法的实用性。
