Effects of Ethyl Carbamate and its Metabolites on the Antibody Response in Splenocyte Cults from Female Balb/C Mice
作者:
JeongTae Cheon,
KimHyun Ju,
ChaShin Woo,
ParkJong Il,
ShinHo Chul,
KimDong Hyun,
HanSang Seop,
RohJung Koo,
期刊:
Immunopharmacology and Immunotoxicology
(Taylor Available online 1996)
卷期:
Volume 18,
issue 1
页码: 91-103
ISSN:0892-3973
年代: 1996
DOI:10.3109/08923979609007112
出版商: Taylor&Francis
数据来源: Taylor
摘要:
AbstractTo 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.
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