ACETAMINOPHEN DOES NOT DECREASE HEPATIC 3'-PHOSPHOADENOSINE 5'-PHOSPHOSULFATE IN MICE

Capacity-limited sulfation of chemicals is thought to be due to the li mited availability of 3'-phosphoadenosine 5'-phosphosulfate (PAPS), th e cosubstrate for sulfation, which in turn is limited by the availabil ity of its precursor, inorganic sulfate. Because this concept evolved from experimental data obtained from rats, and species differences hav e also been reported on acetaminophen (AA) sulfation, this study exami ned the effects of AA on PAPS and sulfate concentrations in mice, anot her widely used experimental animal. RE lowered serum and liver sulfat e concentrations approximately 50% in mice. However, contrary to obser vations in rats, AA (0-600 mg/kg i.p.) did not decrease hepatic PAPS c oncentrations in mice. In summary, these studies demonstrate that AA d ecreases serum and liver sulfate concentrations, but does not decrease hepatic PAPS concentrations in mice. These data indicate that 1) hepa tic sulfation of high dosages of AA in mice is not limited by the avai lability of PAPS, and 2) there are significant species differences in the regulation of AA sulfation between rats and mice.