ISSN:
1432-0738
Schlagwort(e):
Polychlorinated terphenyls
;
Monooxygenases
;
Liver
;
Receptor protein
;
SARS
;
Rat
Quelle:
Springer Online Journal Archives 1860-2000
Thema:
Medizin
Notizen:
Abstract The effects of o-, m- and p-terphenyl, 2,4-dichloro-, 2,4,6-trichloro-, 2,3,5,6-tetrachloro-, 2,3,4,6-tetrachloro-, 2,4,4'",6- tetrachloro- and 2,3,4,5-tetrachloro-p-terphenyl, 2,3,4,5-tetrachloro-m- and o-terphenyl as inducers of hepatic drug-metabolizing enzymes were determined in immature male Wistar rats. o-Terphenyl, 2,4-dichloro-, 2,4,6-trichloro-p-terphenyl and 2,3,4,5-tetrachloro-o-terphenyl induced 4,4′-dimethylamino antipyrine N-demethylase at total dose levels of 300 μmol/kg and the 2,3,4,5-tetrachloro-p-terphenyl induced ethoxyresorufin O-deethylase (EROD). In contrast, none of the other terphenyls or polychlorinated terphenyls (PCTs) induced these enzyme activities. Previous studies have demonstrated that 2,3,4,5-tetrachloro-p-terphenyl did not exhibit a high affinity for the 2,3,7,8-tetrachlorodibenzo-p-trachlorodibenzo-p-dioxin (TCDD) receptor protein (EC50= 6.6×10−6M). In contrast, this study showed that 2,3,4,5-tetrachloro-p-terphenyl was more active than either 2,3,4,5-tetrachloro-o- or m-terphenyl as an inducer of EROD. Moreover, the competitive receptor binding EC50 values for the latter two isomers were 〉 10−5 M and this result was also consistent with their lack of EROD induction activity. Previous studies showed that analysis of the data for a series of 4′-substituted-2,3,4,5-tetrachlorobiphenyls indicated that the p-terphenyl structural moiety (i.e. 4′-substituent = phenyl) did not interact with high affinity with the receptor protein binding site. Since the 2,3,4,5-tetrachloro o- and m-terphenyls are also poor ligands for the receptor protein, this data and results from other studies indicate that PCT congeners (and commercial mixtures) are therefore unlikely to elicit significant 2,3,7,8-TCDD-like biologic or toxic effects in target species.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1007/BF00316331
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