Glutathione-S-transferase (GST) is a family of enzymes involved in the detoxification of toxic and carcinogenic compounds. In the present study, the effect of thioacetamide (TA), a hepatotoxic and hepatocarcinogenic compound, on the activity and expression of GST of Wistar female rats was tested. Animals were treated with a single dose of TA (250 mg/kg) for 12, 24, 48 and 72 hours. GST activity toward the broad substrate 1-chloro-2,4-dinitrobenzene was enhanced by TA. The protein level of the GST classes alpha and mu as well as the mRNA level of several GST subunits were also positively affected by the TA treatment. Female Wistar rats of the same age but from two other different colonies had their GST activity either inhibited or not affected by TA. The basal mRNA level of class alpha and class mu GST was also tested in female Wistar rats obtained from five different sources. Differences in the basal level of class alpha mRNA were observed in rats from at least three different sources, while class mu mRNA level was distinct in two groups of animals.
1 Spira B , Raw I . The effect of thioacetamide on the activity and expression of cytosolic rat liver glutathione-S-transferase . Mol Cell Biochem2000; 211: 103-110 .
2.
2 Jakoby WB . The glutathione S-transferases: a group of multifunctional detoxification proteins . Adv Enzymol Relat Areas Mol Biol1978; 46: 383-414 .
3.
3 Ketterer B . A bird's eye view of the glutathione transferase field . Chem Biol Interact2001; 138: 27-42 .
4.
4 Rushmore TH , King RG , Paulson KE , Pickett CB . Regulation of glutathione S-transferase Ya subunit gene expression: identification of a unique xenobiotic-responsive element controlling inducible expression by planar aromatic compounds . Proc Natl Acad Sci USA1990; 87: 3826-3830 .
5.
5 Nygaard O , Eldjarn L , Nakken KF . Studies on the metabolism of thioacetamide-S-35 in the intact rat . Cancer Res1954; 14: 625-628 .
6.
6 Rees KR , Rowland GF , Varcoe JS . Metabolism of tritiated thioacetamide in rat . Int J Cancer1966; 1: 197-206 .
7.
7 Porter WR , Gudzinowicz MJ , Neal RA . Thioacetamideinduced hepatic necrosis. II. Pharmacokinetics of thioacetamide and thioacetamide-S-oxide in the rat . J Pharmacol Exp Ther1979; 208: 386-391 .
8.
8 Porter WR , Neal RA . Metabolism of thioacetamide and thioacetamide S-oxide by rat liver microsomes . Drug Metab Dispos1978; 6: 379-388 .
9.
9 Stolf AM , D'Abronzo FH , Wang L , Salles JM , Andrade HF, Jr ., Silva SM , Brentani R . Selection of albumin mRNA by thioacetamide . Biochem Biophys Res Commun1976; 72: 1576-1584 .
10.
10 Mesa ML , Carrizosa R , Martinez-Honduvilla C , Benito M , Fabregat I . Changes in rat liver gene expression induced by thioacetamide: protective role of S-adenosyl-L-methionine by a glutathione-dependent mechanism . Hepatology1996; 23: 600-606 .
11.
11 Chakrabartty PK, Schneider WC . Increased activity of rat liver messenger RNA and of albumin messenger RNA modulated by thioacetamide . Cancer Res1978; 38: 2043-2047 .
12.
12 Raw I , Rockwell P . A protein-bound form of thioacetamide in liver nucleoli . Biochem Biophys Res Commun1979; 90: 721-725 .
13.
13 Di Simplicio P . Glutathione and glutathione S-transferases in rat liver and in plasma after carbon tetrachloride and thioacetamide intoxication . Pharmacol Res Commun1982; 14: 909-920 .
14.
14 Diez-Fernandez C , Bosca L , Fernandez-Simon L , Alvarez A , Cascales M . Relationship between genomic Thioacetamide effect on rat GST MTD Bueno and B Spira 437 DNA ploidy and parameters of liver damage during necrosis and regeneration induced by thioacetamide . Hepatology1993; 18: 912-918 .
15.
15 Sanz N , Diez-Fernandez C , Fernandez-Simon L , Alvarez A , Cascales M . Necrogenic and regenerative responses of liver of newly weaned rats against a sublethal dose of thioacetamide . Biochim Biophys Acta1998; 1384: 66-78 .
16.
16 Igarashi T , Satoh T , Iwashita K , Ono S , Ueno K , Kitagawa H . Sex difference in subunit composition of hepatic glutathione S-transferase in rats . J Biochem (Tokyo)1985; 98: 117-123 .
17.
17 Rogiers V , Coecke S , Vandenberghe Y , Morel F , Call-aerts A , Verleye G , Van Bezooijen CF , Guillouzo A , Vercruysse A . Effect of the aging process on the gender and phenobarbital dependent expression of glutathione S-transferase subunits in brown Norway rat liver . Biochem Pharmacol1991; 42: 491-498 .
18.
18 Srivastava PK , Waxman DJ . Sex-dependent expression and growth hormone regulation of class alpha and class mu glutathione S-transferase mRNAs in adult rat liver . Biochem J1993; 294: 159-165 .
19.
19 Ganem LG , Jefcoate CR . Endocrine factors modulate the phenobarbital-mediated induction of cytochromes P450 and phase II enzymes in a similar strain-depen-dent manner . Toxicol Appl Pharmacol1998; 150: 68-75 .
20.
20 Bradford MM . A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding . Anal Biochem1976; 72: 248-254 .
21.
21 Habig WH , Pabst MJ , Jakoby WB . Glutathione S-transferases. The first enzymatic step in mercapturic acid formation . J Biol Chem1974; 249: 7130-7139 .
22.
22 Sambrook J , Russell DW . Molecular cloning: a laboratory manual. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory , 2001.
23.
23 Chomczynski P , Sacchi N . Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction . Anal Biochem1987; 162: 156-159 .
24.
24 Hayes JD , Strange RC . Glutathione S-transferase polymorphisms and their biological consequences . Pharmacology2000; 61: 154-166 .
25.
25 Ingelman-Sundberg M . Genetic polymorphism of human glutathione transferases . Chem Biol Interact2001; 133: 84-86 .
26.
26 Strange RC , Lear JT , Fryer AA . Glutathione S-transferase polymorphisms: influence on susceptibility to cancer . Chem Biol Interact1998; 112: 351-364 .
27.
27 Matsumoto K , Gasser DL . Polymorphism of glutathione S-transferase in laboratory rats . Biochem Genet1983; 21: 1209-1215 .
28.
28 Kumano T , Kimura J , Hayakari M , Yamazaki T , Sawamura D , Tsuchida S . Polymorphism of the glutathione transferase subunit 3 in Sprague Dawley rats involves a reactive cysteine residue . Biochem J2000; 350: 405-412 .
29.
29 Hsu LC , Gould MN . Cloning and characterization of overexpressed genes in the mammary gland of rat strains carrying the mammary carcinoma suppressor (Mcs) gene . Cancer Res1993; 53: 5766-5774 .
30.
30 Biesecker G , Koffler D . Resistance to experimental autoimmune myasthenia gravis in genetically inbred rats. Association with decreased amounts of in situ acetylcholine receptor-antibody complexes . J Immunol1988; 140: 3406-3410 .
31.
31 Rampersaud A , Walz FG, Jr . Polymorphisms of four hepatic cytochromes P-450 in twenty-eight inbred strains of rat . Biochem Genet1987; 25: 527-534 .
32.
32 Larsen MC , Brake PB , Parmar D , Jefcoate CR . The induction of five rat hepatic P450 cytochromes by phenobarbital and similarly acting compounds is regulated by a sexually dimorphic, dietary-dependent endocrine factor that is highly strain specific . Arch Biochem Biophys1994; 315: 24-34 .
33.
33 Berton O , Ramos A , Chaouloff F , Mormde P . Behavioral reactivity to social and nonsocial stimulations: a multivariate analysis of six inbred rat strains . Behav Genet1997; 27: 155-166 .
34.
34 Chanas SA , Jiang Q , McMahon M , McWalter GK , McLellan LI , Elcombe CR , Henderson CJ , Wolf CR , Moffat GJ , Itoh K , Yamamoto M , Hayes JD . Loss of the Nrf2 transcription factor causes a marked reduction in constitutive and inducible expression of the glutathione S-transferase Gsta1, Gsta2, Gstm1, Gstm2, Gstm3 and Gstm4 genes in the livers of male and female mice . Biochem J2002; 365: 405-416 .
