Kennedy A R, Krinsky N I
Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia 19104.
Nutr Cancer. 1994;22(3):219-32. doi: 10.1080/01635589409514348.
We observed that various retinoids (including all-trans-retinoic acid, 13-cis-retinoic acid, and the synthetic retinoid Ro-11-1430) have approximately the same ability to suppress ultraviolet light-induced transformation of C3H10T1/2 cells in vitro. Retinoids also suppress X-ray induced transformation in vitro. Ro-11-1430 has no effect when present for only 1 day after the X-ray exposure but does have a suppressive effect on radiation transformation when present for 5 or 10 days after irradiation. Ro-11-1430 has its major suppressive effect on X-ray transformation when present in irradiated cultures in the confluent stationary phase of growth. Natural beta-carotene (type IV) from carrots, but not synthetic beta-carotene, has the ability to suppress radiation (X-ray)-induced transformation when present for the entire transformation assay period. Natural beta-carotene is without effect on the transformation process when present in irradiated cultures only during confluence. For these retinoids, as well as beta-carotene and canthaxanthin, there is a highly significant suppressive effect on radiation transformation and radiation transformation enhanced by 12-O-tetradecanoylphorbol-13-acetate when the compounds are present at toxic levels; when nontoxic levels are utilized, these compounds have the ability to suppress the yield of transformed cells to approximately one-half of that observed in irradiated cultures in the absence of these compounds. A selective toxicity for transformed cells appeared to exist for the beta-carotene-treated F-17 cells. This apparent selective toxicity was not observed in another line of transformed cells. Cl 16 cells, or in human cells. We observed different uptake patterns of beta-carotene by nontransformed C3H10T1/2 cells, F-17 cells, and Cl 16 cells that may account for the observed apparent selective toxicity of one line of transformed cells (F-17 cells) to beta-carotene.
我们观察到,各种类视黄醇(包括全反式视黄酸、13-顺式视黄酸和合成类视黄醇Ro-11-1430)在体外抑制紫外线诱导的C3H10T1/2细胞转化的能力大致相同。类视黄醇在体外也能抑制X射线诱导的转化。X射线照射后仅存在1天时,Ro-11-1430没有作用,但在照射后5天或10天时对辐射转化具有抑制作用。当处于生长的汇合静止期的照射培养物中时,Ro-11-1430对X射线转化具有主要抑制作用。来自胡萝卜的天然β-胡萝卜素(IV型),而不是合成β-胡萝卜素,在整个转化试验期间存在时具有抑制辐射(X射线)诱导的转化的能力。当仅在汇合期存在于照射培养物中时,天然β-胡萝卜素对转化过程没有影响。对于这些类视黄醇以及β-胡萝卜素和角黄素,当化合物处于毒性水平时,对辐射转化和由12-O-十四烷酰佛波醇-13-乙酸酯增强的辐射转化具有高度显著的抑制作用;当使用无毒水平时,这些化合物能够将转化细胞的产量抑制至在不存在这些化合物的照射培养物中观察到的产量的大约一半。对于β-胡萝卜素处理的F-17细胞,似乎存在对转化细胞的选择性毒性。在另一系转化细胞Cl 16细胞或人类细胞中未观察到这种明显的选择性毒性。我们观察到未转化的C3H10T1/2细胞、F-17细胞和Cl 16细胞对β-胡萝卜素的摄取模式不同,这可能解释了观察到的一系转化细胞(F-17细胞)对β-胡萝卜素的明显选择性毒性。