Prostaglandin H (PGH) synthase (EC (6)(7)(8). However, earlier in vivo studies raised questions whether the pharmacologic activity of aspirin and other nonsteroidal antiinflammatory drugs is entirely mediated through this mechanism (1, 9). PGH synthase has been found to have a rapid turnover rate (half-life of 5-6 min) in the few tissues examined (10, 11). Cytokines and phorbol diesters are known to induce synthesis of the enzyme, thereby raising the level of PGH synthase protein severalfold over the basal levels (11)(12)(13)(14). In this communication, we report results of studies with cultured endothelial cells that indicate that aspirin and salicylate are able to inhibit the de novo synthesis of the enzyme by action at the level of gene expression.

3-Hydroxypropylmercapturic acid [3-OHPrMCA, S-(3-hydroxypropyl)-N-acetyl-L-cysteine] was quantitatively measured by high-performance liquid chromatography (HPLC) in the urine of rats given allylamine.HCl (5, 25, 50, 100 and 150 mg kg-1), acrolein (13 mg kg-1), allylalcohol (64 mg kg-1), allylchloride (76 mg kg-1), allylbromide (120 mg kg-1), allylcyanide (115 mg) and cyclophosphamide (160 mg kg-1) by gavage in water. 3-OHPrMCA was measured by HPLC in 24-h urine collections; the lower detection limit was 1.25 micrograms or 5.6 nmol ml-1. Various doses of allylamine resulted in 3-OHPrMCA excretion at a fairly constant percentage of the dose, ca. 44-48% at 0-24 h and 3% at 24-48 h, indicating rapid metabolism through glutathione conjugation in the first 24h. Similarly, 3-OHPrMCA was recovered in the urine of rats given acrolein (78.5%), allylalcohol (28.3%), allylchloride (21.5%), allylbromide (3.0%), allylcyanide (3.7%) and cyclophosphamide (2.6%). These data indicate that 3-OHPrMCA can be used as a marker of exposure to allylic and other compounds that lead to the metabolic formation of acrolein.

for valuable discussions and L. J. M. van de Ven and P. van Dael (Nijmegen) for the technical assistance in recording the NMR spectra.Registry No. 1, 91237-85-3; 2, 96259-12-0; cAMP, 60-92-4; trimethyl phosphite, 121-45-9; dimethylamine, 124-40-3; dimethoxy(dimethylamino)phosphine, 20217-54-3; 2',3'-0-isopropylideneadenosine, 362-75-4; 2',3'-0-isopropylideneadenosin-5'-yl dimethyl phosphite, 96259-13-1.

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