Glutathione S-transferase-P (GST-P) is considered to be an accurate marker for hepatocellular carcinoma in rodents. In rat hepatocarcinogensis, GST-P can be detected in altered hyperplastic foci before the appearance of hepatocellular carcinoma. Ito and coworkers (Toxicol, Pathol., 17:630, 1989) have developed an in vivo assay system for GST-P induction, and reported it to be highly effective for identifying hepatocarcinogens. The Ito procedure for inducing and measuring GST-P induction in rats, which requires partial hepatectomy, is being compared with a simpler procedure that does not require partial hepatectomy. We have also adapted the GST-P assay system to cells in vitro in order to assess the predictivity of GST-P induction in these cells for liver carcinogenesis in rodents. GST-P can be induced by chemicals in a normal rat liver cell line (WB cells) aid a transformed line (GP6 cells) derived from WB cells. The levels of GST-P can be quantitated by spectrophotometry. Mutagenic and nonmutagenic hepatocarcinogens and noncarcinogens (including N-nitro-N-methylurea: dimethylbenzanthracene: 2- and 4-acetylaminofluorene: butylated hydroxyanisole: butylated hydroxytoluene: phenobarbitol: dimethyl sulfoxide: 2, 4- and 2, 6-diaminotoluene) are being evaluated for their ability to induce GST-P in the WB and GP-6 cell lines.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES021159-01
Application #
3855874
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1991
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code