As_2O_3、MNNG和B(a)P对人胎儿及大鼠气管上皮的致癌前病变作用

器官培养能保持组织相对正常的结构与功能,可用于研究致癌物的代谢和癌症的发生,尤其是人体组织器官培养,对研究各种外界因子在人体组织癌变过程中的作用具有特殊意义。流行病学研究表明,砷对人体肺组织具有致痛作用;细胞遗传学研究发现,砷能导致哺乳类动物的染色体损伤,但砷对动物组织的致癌作用尚未得到确证。本实验采用器官培养法,研究三氧化二砷(As_2O_3)及已知致癌物N-甲基-N′     

As2O3,MNNG和B（a）P对人胎儿及大鼠气管上皮的致癌...

The effects of As2O3, MNNG and B(a)P on epithelia of human fetal tracheae and rat tracheae in organ culture were studied. In human fetal trachea, a small dose of arsenic (1 mumol As) induced hyperplasia of the epithelium; 3-9 mumol As induced hyperplasia and cellular atypia in the epithelium, and hyperplasia and squamous metaplasia in the adenoepithelium. Similar effects were not observed in rat tracheae. MNNG and B(a)P induced hyperplasia, squamous metaplasia and dysplasia in human fetal tracheal and rat tracheal epithelia respectively, and MNNG also induced hyperplasia and squamous metaplasia in human fetal tracheal adenoepithelium. The data suggest that 1) arsenic may be carcinogenic to the human respiratory tract but not to the rat; and 2) human tissues in organ culture are very useful for detecting carcinogens and for studying carcinogenesis.     

砷对人二倍体细胞的遗传毒性作用

本研究首次用一系列细胞遗传毒理学指标如SCE、DNA含成抑制、UDS、DNA单链断裂和DNA蛋白质交联来检测砷对人二倍体细胞DNA损伤和修复作用。结果表明:①As_2O_3(As1×10~(-8)-10~(-6)M)明显诱导人外周血淋巴细胞SCE频率,且呈剂量效应关系;②一定剂量砷能抑制2BS细胞DNA合成、诱导UDS和DNA蛋白质交联和单链断裂,表明砷对DNA有一定程度损伤作用;③3μM砷可能细胞毒性较小,而与蛋白质结合量较大,故诱导的DNA蛋白质交联作用最大,我们认为砷对DNA损伤作用较弱,可能不是其致癌作用的主要原因。与DNA损伤效应不同,砷是断裂剂,引起染色体断裂,可能因易位到另外染色体的某些基因区域上,形成基因重排、激活癌基因而致癌。