Abstract
Acetaminophen is used clinically as an analgesic and antipyretic drug. Although acetaminophen is safe at therapeutic doses, it produces
hepatic injury in both human and experimental animals, and also induces morphological transformation in cultured cells when given in
excessive doses. The hepatic injury produced by acetaminophen is generally thought to be initiated by a reactive metabolite of
acetaminophen, N-acetyl-p-benzo-quinoneiniine (NAPQI), formed by cytochrome P450. NAPQI is initially detoxified by conjugation to
reduce glutathione (GSH). A primary cellular target of Acetaminophen is GSH, which is an extremely important cellular antioxidant. A
marked cellular GSH level change following the exposure to arsenic has been reported, which is inversely related to the intracellular
accumulation of arsenic. In this study, we have investigated the effects of acetaminophen on the cellular total GSH level in different tumor
and normal cell lines. Five different cell lines of human hepatic carcinoma (HePG2), human lung adenocarcinoma (A549), human ovarian
carcinoma (SKOV3), dog kidney (LLCPK1) and Chiness hamster ovary (CHO) cell lines were exposed to the IC50 concentrations of
acetaminophen for two hours. Acetaminophen cytotoxicity was measured using clonogenic assay, and the total cellular GSH level were
analyzed using a photo metrically assay. Our results showed that acetaminophen had different degrees of cytotoxicities on different cell lines
as shown by IC50 values; 18.6 for HepG2, 4.16 for A549, 5.01 for SKOV3, 5.6 for LLCPK1, and 16.7 for CHO cell lines. According to our
results, GSH level alterations after exposure to acetaminophen were also different for different cell lines; 24.21 for HepG2, 778.21 for A549,
977 for SKOV3, 1367.3 for LLCPK1, and 312.43 for CHO cell lines. It is concluded that acetaminophen undergoes different metabolic
pathways in different cell lines that produces various species which might or might not bind to GSH. Although cells would increase their
cellular GSH content after exposure to acetaminophen, but the superiority of either pathway in each cell line would determine the GSH
consumption and therefore the cellular protection against the cytotoxicity of acetaminophen in each cell line.
