Effects of ethyl carbamate and its metabolites on the antibody response in splenocyte cultures from female Balb/C mice.
To investigate a possible role by cytochrome P450 (P450) in ethyl carbamate-induced immunosuppression, an attempt to assess the ability of ethyl carbamate, its metabolites produced by P450 (i.e., ethyl N-hydroxycarbamate and vinyl carbamate), and methyl carbamate to suppress the polyclonal antibody response induced by bacterial lipopolysaccharide was made in splenocyte cultures isolated from female Balb/C mice. The results showed that vinyl carbamate and ethyl N-hydroxycarbamate were more immunosuppressive compared to ethyl carbamate. A structurally related analogue, methyl carbamate, did not suppress the antibody response. These results indicate that metabolism of ethyl carbamate by P450 may produce more immunosuppressive metabolites as in ethyl carbamate-induced carcinogenicity. A pre-incubation study with phenobarbital-induced liver microsomes in the presence of NADPH-generating system showed that the antibody response was suppressed by ethyl carbamate when splenocytes were pre-incubated with ethyl carbamate and microsomes simultaneously. Moreover, the suppression was completely recovered by the addition of a P450 inhibitor, aminoacetonitrile, in the pre-incubation. Taken together, the present results indicate that metabolism of ethyl carbamate by P450 enzyme(s) may be an important pathway to cause immunosuppression.
Jeong
T C
TC
Toxicology Research Center, Korea Research Institute of Chemical Technology, Taejon.
Kim
H J
HJ
Cha
S W
SW
Park
J I
JI
Shin
H C
HC
Kim
D H
DH
Han
S S
SS
Roh
J K
JK
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis* / Q000187:drug effects; D000921:Antibody-Producing Cells / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects; D005260:Female; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D014520:Urethane / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology*
D000907:Antibodies, Bacterial; D008070:Lipopolysaccharides; D014520:Urethane; D003577:Cytochrome P-450 Enzyme System