Lambert B, Andersson B, Bastlova T, Hou S M, Hellgren D, Kolman A
Environmental Medicine Unit, Karolinska Institutet, Huddinge, Sweden.
Environ Health Perspect. 1994 Oct;102 Suppl 4(Suppl 4):135-8. doi: 10.1289/ehp.94102s4135.
Provisional mutational spectra at the hypoxanthine phosphoribosyl transferase (HPRT) locus in vitro have been worked out for acetaldehyde (AA) and benzo[a]pyrene diolepoxide (BPDE) in human (T)-lymphocytes and for ethylene oxide (EtO) in human diploid fibroblasts using Southern blotting and polymerase chain reaction (PCR)-based DNA sequencing techniques. The results indicate that large genomic deletions are the predominating hprt mutations caused by AA and EO, whereas BPDE induces point mutations that are mainly GC > TA transversions. The mutational spectra induced by the three agents are clearly different from the background spectrum in human T-cells. Thus, the hprt locus is a useful target for the study of chemical-specific mutational events that may help identify causes of background mutation in human cells in vivo.
利用Southern印迹法和基于聚合酶链反应(PCR)的DNA测序技术,已得出人(T)淋巴细胞中乙醛(AA)和苯并[a]芘二环氧物(BPDE)以及人二倍体成纤维细胞中环氧乙烷(EtO)在次黄嘌呤磷酸核糖转移酶(HPRT)基因座的临时突变谱。结果表明,大片段基因组缺失是由AA和环氧乙烷引起的主要hprt突变,而BPDE诱导的点突变主要是GC>TA颠换。这三种试剂诱导的突变谱明显不同于人T细胞中的背景谱。因此,hprt基因座是研究化学特异性突变事件的有用靶点,这可能有助于确定体内人类细胞背景突变的原因。