江南大学第6章农药残留.pptVIP

Structure-activity relationships appear to provide a reasonably good basis to predict carcinogenicity for some categories of compounds, which are characterized by specific structures. 依靠化学物结构----活性关系预测具有特定结构化学物的致癌性 It has also become clear that a strong association exists between mutagenicity and the extent and sites of tumorigenicity. 致肿瘤原所处范围及位置影响诱变性 第一百二十七页，共一百八十九页。 Four stages of cancer形成癌症的四个阶段 引发 (initiation) 促进 (promotion) 发展 (progression) 转移 (metastasis) 第一百二十八页，共一百八十九页。 引发 (initiation) irreversible (even small doses have an irreversible and thus an additive effect) 不可逆 (即使只有非常少的剂量也会造成不可逆效应 ) a dose-related phenomenon 与剂量有关 does not exhibit a readily measurable threshold 不存在阈值 (阈值指当所用的剂量低于该值时不会产生某种效应 ) 第一百二十九页，共一百八十九页。 Dose 剂量 Low doses of initiating carcinogens thus present a low but defined risk. 低剂量的致癌引发物表现出明显的低程度危害。 The extent of this risk cannot be determined but only assessed with various methods of extrapolation. 无法测定，只有采用各种外推手段进行评估 第一百三十页，共一百八十九页。 The condition of initiation引发的条件 irreversibility and fixation of initiation by cell division 细胞分裂可造成引发过程的不可逆性及“固化” the process must occur within a relatively short time of replicative DNA synthesis and cell division 只有DNA复制和细胞分裂在很短的时间内完成，引发作用才会真正起作用。 第一百三十一页，共一百八十九页。 Damaged genes 损伤的基因 1、Key genes involved in the regulation of cell growth and differentiation 参与控制细胞增殖和分化的关键性基因 2、 ras family protooncogenes and the p53 tumor-suppressor gene ras族原遗传致癌基因和p53肿瘤抑制基因 第一百三十二页，共一百八十九页。 For example, application of the genotoxin dimethylbenzanthracene (DMBA) to mouse skin is frequently associated with a specific mutation in codon 61 of the H-ras oncogene. 例如，将二甲基苯并蒽(DMBA)作用于小鼠皮肤时专门使H-ras遗传致癌基因密码子61产生突变。 第一百三十三页，共一百八十九页。 In vitro studies 体外试验 useful for determining the mechanism of toxicity 确定毒性机制 e.g., covalent binding to cellular macromolecules 与细胞大分子的共价结合 affinity to certain specific receptor macro molecules 与某些特定的受体大分子的亲和作用 第