用于检测间接作用致断裂剂的MCL-5细胞与人类淋巴细胞的比较研究。

Comparative studies of MCL-5 cells and human lymphocytes for detecting indirect-acting clastogens.

作者信息

Yamakage K, Kusakabe H, Tanaka N

机构信息

Department of Cellular and Genetic Toxicology, Hatano Research Institute, Food and Drug Safety Center, Hadano, Kanagawa, Japan.

出版信息

Mutat Res. 1998 Jan 13;412(1):55-61. doi: 10.1016/s1383-5718(97)00170-8.

DOI:10.1016/s1383-5718(97)00170-8

PMID:9508364

Abstract

The MCL-5 cell line was established from human lymphoblastoid TK+/- cells transfected with cDNAs of human cytochrome P450s (CYP1A2, CYP2A6, CYP2E1, and CYP3A4) and microsomal epoxide hydrolase. The TK+/- cells constitutively express a relatively high level of endogenous CYP1A1. To study metabolic activities to indirect-acting clastogens, MCL-5 cells were treated with four clastogens, i.e. aflatoxin B1 (AFB1), diethylnitrosamine (DEN), cyclophosphamide (CPA), and 7,12-dimethylbenz[a]anthracene (DMBA). Human lymphocytes from peripheral blood were used as control cells under the assay conditions with or without induced rat liver metabolic activation (S9). All chemicals tested without S9 induced chromosomal aberrations (CA) in MCL-5 cells but not in human lymphocytes. All chemicals induced CA in both cell types in the presence of S9.

摘要

MCL-5细胞系是从用人细胞色素P450（CYP1A2、CYP2A6、CYP2E1和CYP3A4）及微粒体环氧化物水解酶的cDNA转染的人淋巴母细胞样TK+/-细胞建立而来。TK+/-细胞组成性地表达相对高水平的内源性CYP1A1。为了研究对间接作用致断裂剂的代谢活性，用四种致断裂剂，即黄曲霉毒素B1（AFB1）、二乙基亚硝胺（DEN）、环磷酰胺（CPA）和7,12-二甲基苯并[a]蒽（DMBA）处理MCL-5细胞。在有或没有诱导的大鼠肝脏代谢活化（S9）的检测条件下，来自外周血的人淋巴细胞用作对照细胞。所有未经S9检测的化学物质在MCL-5细胞中诱导了染色体畸变（CA），但在人淋巴细胞中未诱导。在有S9的情况下，所有化学物质在两种细胞类型中均诱导了CA。