Metabolism of terephthalic acid and its effects on CYP4B1 induction.
OBJECTIVE
To investgate the metabolism of terephthalic acid (TPA) in rats and its mechanism. Methods Metabolism was evaluated by incubating sodium terephthalate (NaTPA) with rat normal liver microsomes, or with microsomes pretreated by phenobarbital sodium, or with 3-methycholanthrene, or with diet control following a NADPH-generating system. The determination was performed by high performance liquid chromatography (HPLC), and the mutagenic activation was analyzed by umu tester strain Salmonella typhimurium NM2009. Expression of CYP4B1 mRNA was detected by RT-PCR. Results The amount of NaTPA (12.5-200 micromol x L(-1)) detected by HPLC did not decrease in microsomes induced by NADPH-generating system. Incubation of TPA (0.025-0.1 mmol x L(-1)) with induced or noninduced liver microsomes in an NM2009 umu response system did not show any mutagenic activation. TPA exposure increased the expression of CYP4B 1 mRNA in rat liver, kidney, and bladder.


CONCLUSIONS
Lack of metabolism of TPA in liver and negative genotoxic data from NM2009 study are consistent with other previous short-term tests, suggesting that the carcinogenesis in TPA feeding animals is not directly interfered with TPA itself and/or its metabolites.
Dai
Gui-Dong
GD
Institute of Toxicology, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, Jiangsu, China. daiguidong@163.com
Cui
Lun-Biao
LB
Song
Ling
L
Zhao
Ren-Zhen
RZ
Chen
Jian-Feng
JF
Wang
Yu-Bang
YB
Chang
Hebron C
HC
Wang
Xin-Ru
XR