DOSE-RESPONSE RELATIONSHIP IN MULTISTAGE CARCINOGENESIS - PROMOTERS
DOSE-RESPONSE RELATIONSHIP IN MULTISTAGE CARCINOGENESIS - PROMOTERS
复制标题
DOI：
10.1289/ehp.94102s1255
复制
发表时间：
1994-01-01
影响因子：
10.4
通讯作者：
SETZER, RW
中科院分区：
文献类型：
--
作者：
KITCHIN, KT;BROWN, JL;SETZER, RW
已发表的多阶段致癌启动子的剂量-反应曲线选择符合长研究时间、多剂量和低剂量的综合标准。在大鼠肝脏中，选择了7种不同的启动子（苯巴比妥、2,3,7,8-四氯二苯并对二恶英[TCDD]、氯芬a- 50（一种多氯联苯）、α -、β -和γ -六氯环己烷[HCH]和氯仿）进行了12项剂量反应研究。对这些启动子进行了7-86周的研究，并确定了肝灶改变或肝癌。剂量从1ng （TCDD）到400mg（氯仿）不等。在小鼠皮肤中，选取了4种启动子（12- o -十四烷醇-13-乙酸酯[TPA]、蒽醌、大黄素和2,6-二叔丁基-4-羟基过氧基-2,5-环己二烯酮[bhhtooh]）的10个剂量效应研究。在这些小鼠皮肤研究中，剂量范围为每只小鼠0.425毫摩尔（TPA）至20,000毫摩尔（bhhtooh）。促进剂在皮肤上的使用时间在15到60周之间。皮肤乳头状瘤或癌均被确定。剂量-反应关系是基于促进剂的摩尔数，完全有效促进剂量的百分比，急性口服大鼠LD的百分比（50）。测定了剂量-反应曲线的凹凸度。现有的剂量-反应数据在生物学癌症风险评估模型的未来研究需求的基础上进行了批评和讨论。
Published dose-response curves of promoters of multistage carcinogenesis were selected that met the combined criteria of long study times, multiple doses, and low doses. In rat liver, 12 dose-response studies of 7 different promoters (phenobarbital, 2,3,7,8-tetrachlorodibenzo-p-dioxin [TCDD], clophen A-50 (a polychlorinated biphenyl), alpha-, beta-, and gamma-hexachlorocyclohexane [HCH], and chloroform) were selected. These promoters were studied for 7-86 weeks and either altered hepatic foci or hepatic cancer were determined. The doses ranged from 1 ng (TCDD) to 400 mg (chloroform). In mouse skin, 10 dose-response studies of 4 promoters (12-O-tetradecanoylphorbol-13-acetate [TPA], anthralin, chrysarobin, and 2,6-di-tert-butyl-4-hydroperoxyl-2,5-cyclohexadienone [BHTOOH]) were selected. In these mouse skin studies the doses ranged from 0.425 nmole (TPA) to 20,000 mnole (BHTOOH) per mouse. The length of time promoters were applied to the skin varied between 15 and 60 weeks. Either skin papillomas or carcinomas were determined. The dose-response relationships are presented on the basis of moles of promoter, percentage of the fully effective promoting dose, of percentage of the acute oral rat LD(50). The degree of concavity of the dose-response curves was determined. The available dose-response data are critiqued and discussed on the basis of future research needs for biologically based cancer risk assessment models.