Wille J J, Chopra D P
Kettering-Meyer Laboratoires, Southern Research Institute, Birmingham, AL 35255.
Cancer Lett. 1988 Jun 30;40(3):235-46. doi: 10.1016/0304-3835(88)90082-1.
In a defined culture system for hamster tracheal explants, the activity of 12 different retinoids was evaluated for reversal of keratinization induced by exposure to the carcinogen, benzo[alpha]pyrene (BP-HTOC assay). The effects of retinoids in this system were compared to those in a defined culture system for tracheal explants from vitamin A-deficient hamsters (standard-HTOC assay). In both assays, all-trans-retinoic acid (RA) and 13-cis-RA were the most active retinoids. For RA and 13-cis-RA, the values of ED50 determined in the BP-HTOC bioassay were 4 x 10(-12) and 1 x 10(-11) M, respectively, whereas the corresponding values in the standard HTOC assay were 2 x 10(-11) and 3.3 x 10(-10) M. For all 12 retinoids, the ED50 values from the BP-HTOC were lower than those from the standard-HTOC assay, and there was also a statistically significant correlation between the rank-ordering of ED50 values from the 2 assays. Among 3 N-(retinoyl)amino acids examined in both assays, N-(retinoyl)leucine was the most active, N-(retinoyl)phenylalanine the least active, and N-(retinoyl)alanine intermediate. Among a novel series of bifunctional retinoic acid analogues, the dicarboxyl derivative was the most active. On the basis of these results, the BP-HTOC assay appears to be one of the most sensitive assays for retinoids yet developed. This assay is an appropriate model for evaluating the chemopreventive potential of new retinoids in vitro.
在仓鼠气管外植体的特定培养系统中，评估了12种不同类视黄醇对由致癌物苯并[a]芘诱导的角质化逆转的活性（BP-HTOC测定法）。将该系统中类视黄醇的作用与维生素A缺乏仓鼠气管外植体的特定培养系统中的作用进行了比较（标准-HTOC测定法）。在这两种测定法中，全反式视黄酸（RA）和13-顺式视黄酸是活性最高的类视黄醇。对于RA和13-顺式视黄酸，在BP-HTOC生物测定法中测定的ED50值分别为4×10^(-12)和1×10^(-11) M，而在标准HTOC测定法中的相应值为2×10^(-11)和3.3×10^(-10) M。对于所有12种类视黄醇，BP-HTOC的ED50值低于标准-HTOC测定法的ED50值，并且两种测定法的ED50值排序之间也存在统计学上的显著相关性。在两种测定法中检测的3种N-(视黄酰基)氨基酸中，N-(视黄酰基)亮氨酸活性最高，N-(视黄酰基)苯丙氨酸活性最低，N-(视黄酰基)丙氨酸居中。在一系列新型双功能视黄酸类似物中，二羧基衍生物活性最高。基于这些结果，BP-HTOC测定法似乎是迄今开发的对类视黄醇最敏感的测定法之一。该测定法是体外评估新型类视黄醇化学预防潜力的合适模型。
