Student Research: Dana Lorene Stahl
, , 1993
Faculty Advisor: David L. Eaton
Regulation of Rat Glutathione S-Transferase Isozyme Expression by Cytochrome P450 Inducing Agents and Diquat
Glutathione S-Transferases (GSTs) are a multi-gene family of enzymes which act in the detoxification of many environmentally and occupationally important carcinogens. Dietary items such as broccoli, brussels sprouts, onions and garlic are known to protect against cancer incidence; each of these vegetables contains compounds that increase GST levels. The GST family of enzymes is composed of alpha (Ya1, Ya2, Yc1 and Yk), mu (Yb1, Yb2 and Yb3), pi (Yf) and theta (Yrs and Ytheta5) classes. THe isozymes within each class differ in their ability to detoxify chemicals. Previous studies have shown that specific isozymes may be responsible for the resistance of animals to cerrtain chemical carcinogens. Several chemical compounds that are known to induce cytochrome P450 isozymes via receptor mediated interaction with 5'-regulatory elements were examined for their ability to induce GST messenger RNA (mRNA) levels in the liver, kidney, lung and intestine of rats. GST mRNA levels were also measured following diquat induced oxidative stress, in order to provide a comparison of enzyme regulation in response to a pro-carcinogenic chemical response. 3-Methylcholanthrene, pregnenolone-16a-carbonitrile and phenobarbital promoted slight increases in mRNA expression of several GST isozymes, although effects varied between isozymes and across tissues. Diquat caused decreases in the mRNA expression of all constitutively expressed isozymes in the liver (Ya1, Ya2, Yc1, Yb1 and Yb2) while increasing isozyme expression (Ya1, Ya2, Yc1, Yb1, Yb2, Yf and Yrs) in the kidney. This study demonstrates that a variety of chemicals, including inducers of cytochrome P450 expression and ocidative stress, produce differential expression of GST isozymes.