摘要
用人胎支气管上皮细明研究了苯并(a)芘(BaP)5种代谢物诱发程序外DNA合成和微核形成的能力。结果显示,除syn-BPDE外,所有代谢物都能诱发人支气管上皮细胞的UDS和MN,但anti-BPDE的作用最强,它可能是BaP的一种最终致癌代谢物,在人类肺癌的病因中起重要作用。
Four BaP metabolites (3-OH-BP, 9-OH-BP, anti-BPDE, syn-BPDE)were assessed for theirpotential to induce unscheduled DNA synthesis (UDS) and micronuclei in mnnanfetal tracheal epithelial (HFTE) cells. HFTE cells were cultured with MCDB153 medium oncover slices. In UDS assay, HFTE cells were treated with ^(14)C-TdR (0.01p Ci/ml) for 72h,hen ~3H-TdR(1μ Ci/ml) and BaP metabolites for another 24h. Radioactivity was measuredwith LS6000 liquid scintillation system. For measurement of micronuclei, HFTE cells weretexposed to metabolites and cytochalasin B (3.0μg/ml) for 24h, then fixed with solution ofmethanol: acetae acid(2:1) and staned with Giemsa.Micronuclei were scored in cytokinesis-blocked cells. The results showed that all metabolites except syn-BPDE can induce UDS andmicronuclei in HFTE cells. There is a linear correlation between metabolite concentration andUDS level and number of induced micronuclei. Anti-BPDE can induce UDS and micronucleiin a relatively high level, compared with 3-OH-BP and 9-OH-BP. Althrough 3-OH-BP and9-OH-BP are not active metabolites perse, they can be metabolized to anti-BPDE. Syn-BPDEis completely different from anti-BPDE in stereo-structure and is not suitable to bind withDNA. It is suggested that DNA of HFTE cells can be damaged by BaP metabolites and DNAdamage is related to stereo-structure of BaP metabolites.
出处
《卫生毒理学杂志》
CSCD
1993年第4期224-226,231,共4页
Journal of Health Toxicology
基金
国家自然科学基金资助项目的分题之一(项目编号:39070903)
关键词
苯并(A)芘
代谢物
气管上皮细胞
肺癌
致癌机理
Benz(a) pyrene
Metabolites
Human fetal tracheal epithelial cells
UDS
Micronucleus
