TY - JOUR
T1 - CYP2E1 regulation by benzene and other small organic chemicals in rat liver and peripheral lymphocytes
AU - González-Jasso, Eva
AU - López, Tomás
AU - Lucas, Daniele
AU - Berthou, Francois
AU - Manno, Maurizio
AU - Ortega, Arturo
AU - Albores, Arnulfo
N1 - Funding Information:
This work was supported by European Commission INCO-DC contract N. ERB IC18-CT980341 and CONACyT project N. M0061-M9602. EGJ received a grant from CONACyT.
PY - 2003/9/15
Y1 - 2003/9/15
N2 - The inducibility of CYP2E1 was investigated in liver and peripheral lymphocytes of rats treated with benzene (0-10 mmol/kg body weight (bw), daily for 3 days, i.p., or 0 and 5 mmol/kgbw, daily for 14 days, i.p.) or toluene (0 and 5 mmol/kgbw, daily for 3 days, i.p.) and compared with that of pyridine (5 mmol/kgbw, i.p.) or acetone (5% in drinking water) both daily for 3 days. Acute benzene treatment (5 mmol/kgbw) increased both CYP2E1 apo-protein (2-fold) and p-nitrophenol hydroxylase (p-NPH) activity (1.4-fold) in liver, and CYP2E1 mRNA in both liver (2.2-fold) and peripheral lymphocytes (2.9-fold). The response to toluene was qualitatively similar, although smaller than that to benzene. As expected, acetone and pyridine treatments resulted in a 2- to 3-fold increase of p-NPH activity and CYP2E1 apo-protein content in liver, but not the mRNA levels. In addition, acute benzene and acetone treatments increased the 6-hydroxychlorzoxazone/chlorzoxazone metabolic ratio 1.6- and 3.1-fold, respectively. The subchronic treatment with benzene increased CYP2E1 mRNA and apo-protein from days 2 and 3 to day 14, respectively, whereas the enzyme activity increased transiently on days 3 and 5 only. These results show that acute/subacute benzene and acute toluene treatments induce CYP2E1 expression probably through a similar mechanism which might be different from that of pyridine or acetone, in that the former increase mRNA levels, both in liver and in peripheral lymphocytes, whereas the latter stabilized the apo-protein.
AB - The inducibility of CYP2E1 was investigated in liver and peripheral lymphocytes of rats treated with benzene (0-10 mmol/kg body weight (bw), daily for 3 days, i.p., or 0 and 5 mmol/kgbw, daily for 14 days, i.p.) or toluene (0 and 5 mmol/kgbw, daily for 3 days, i.p.) and compared with that of pyridine (5 mmol/kgbw, i.p.) or acetone (5% in drinking water) both daily for 3 days. Acute benzene treatment (5 mmol/kgbw) increased both CYP2E1 apo-protein (2-fold) and p-nitrophenol hydroxylase (p-NPH) activity (1.4-fold) in liver, and CYP2E1 mRNA in both liver (2.2-fold) and peripheral lymphocytes (2.9-fold). The response to toluene was qualitatively similar, although smaller than that to benzene. As expected, acetone and pyridine treatments resulted in a 2- to 3-fold increase of p-NPH activity and CYP2E1 apo-protein content in liver, but not the mRNA levels. In addition, acute benzene and acetone treatments increased the 6-hydroxychlorzoxazone/chlorzoxazone metabolic ratio 1.6- and 3.1-fold, respectively. The subchronic treatment with benzene increased CYP2E1 mRNA and apo-protein from days 2 and 3 to day 14, respectively, whereas the enzyme activity increased transiently on days 3 and 5 only. These results show that acute/subacute benzene and acute toluene treatments induce CYP2E1 expression probably through a similar mechanism which might be different from that of pyridine or acetone, in that the former increase mRNA levels, both in liver and in peripheral lymphocytes, whereas the latter stabilized the apo-protein.
KW - Benzene
KW - CYP2E1
KW - Liver
KW - Lymphocytes
KW - Toluene
UR - http://www.scopus.com/inward/record.url?scp=0041659134&partnerID=8YFLogxK
U2 - 10.1016/S0378-4274(02)00337-5
DO - 10.1016/S0378-4274(02)00337-5
M3 - Artículo
C2 - 12919724
AN - SCOPUS:0041659134
SN - 0378-4274
VL - 144
SP - 55
EP - 67
JO - Toxicology Letters
JF - Toxicology Letters
IS - 1
ER -