MUTAGENICITY AND EFFECT ON GAP JUNCTIONAL INTERCELLULAR COMMUNICATION OF 4,4'-METHYLENEBIS(2-CHLOROANILINE) AND ITS OXIDIZED METABOLITES

被引:5
作者
KUSLIKIS, BI
TROSKO, JE
BRASELTON, WE
机构
[1] MICHIGAN STATE UNIV,DEPT PHARMACOL & TOXICOL,E LANSING,MI 48824
[2] MICHIGAN STATE UNIV,DEPT PEDIAT & HUMAN DEV,E LANSING,MI 48824
关键词
D O I
10.1093/mutage/6.1.19
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Oxidized metabolites of 4,4'-methylenebis(2-chloroaniline) (MBOCA) were tested for direct mutagenicity in a Salmonella typhimurium assay and for effects on gap-junctional communication of WB-F344 rat liver cells. The mutagenicities of the N-hydroxy, mononitroso and omicron-hydroxy (ring) metabolites of MBOCA were assayed without adding activating enzyme systems, using the frame-shift sensitive strain TA98 and the base pair substitution sensitive strain TA100. The mutagenicity of the hydroxylamine was demonstrated by a linear increase in the formation of mutant colonies in both strains, with a formation of two revertants/nmol by TA98 and 21 revertants/nmol by TA100. The mononitroso metabolite showed a slight positive effect on TA100, but effects were masked by its cytotoxicity towards this strain. This metabolite was neither mutagenic nor cytotoxic to TA98. The omicron-hydroxy and the dinitroso metabolites were negative for mutagenicity at concentrations up to 50 and 500-mu-g/plate, respectively. The effects of parent MBOCA and N-hydroxy, mononitroso and omicron-hydroxy metabolites on cell-cell communication were determined by a scrape loading/fluorescent dye transfer technique. Cytotoxicity was assessed by determination of colony-forming efficiency and lactate dehydrogenase release. MBOCA itself caused an inhibition of dye transfer at concentrations of 7.5, 11.3 and 15 nmol/ml, whereas measures of cytotoxicity were not seen until 15 and 30 nmol/ml for LDH release and plating efficiency, respectively. None of the oxidized metabolites were active in inhibiting dye transfer at non-cytotoxic concentrations.
引用
收藏
页码:19 / 24
页数:6
相关论文
共 37 条
[1]  
BUTLER MA, 1989, CANCER RES, V49, P25
[2]  
CHEN TH, 1989, DRUG METAB DISPOS, V17, P406
[3]  
DUCOS P, 1984, INT ARCH OCC ENV HEA, V55, P159
[4]   SCRAPE-LOADING AND DYE TRANSFER - A RAPID AND SIMPLE TECHNIQUE TO STUDY GAP JUNCTIONAL INTERCELLULAR COMMUNICATION [J].
ELFOULY, MH ;
TROSKO, JE ;
CHANG, CC .
EXPERIMENTAL CELL RESEARCH, 1987, 168 (02) :422-430
[5]  
ENOMOTO T, 1981, P NATL ACAD SCI-BIOL, V78, P5628, DOI 10.1073/pnas.78.9.5628
[6]   ANCHORED CELL ANALYSIS SORTING COUPLED WITH THE SCRAPE LOADING DYE TRANSFER TECHNIQUE TO QUANTIFY INHIBITION OF GAP JUNCTIONAL INTERCELLULAR COMMUNICATION IN WB-F344 CELLS BY 2,2',4,4',5,5'-HEXABROMOBIPHENYL [J].
EVANS, MG ;
ELFOULY, MH ;
TROSKO, JE ;
SLEIGHT, SD .
JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH, 1988, 24 (02) :261-271
[7]  
Farmer P B, 1981, J Appl Toxicol, V1, P317, DOI 10.1002/jat.2550010610
[8]   MUTAGENICITY OF 4,4'-METHYLENE-BIS-(2-CHLOROANILINE) MOCA AND ITS N-ACETYL DERIVATIVES IN S-TYPHIMURIUM [J].
HESBERT, A ;
BOTTIN, MC ;
DECEAURRIZ, J .
INTERNATIONAL ARCHIVES OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH, 1985, 55 (02) :169-174
[9]  
KOMMINENI C, 1978, J ENVIRON PATHOL TOX, V2, P149
[10]  
LOWENSTEIN WR, 1979, BIOCHIM BIOPHYS ACTA, V560, P1