Mutagenicity studies on paracetamol in human volunteers. I. Cytogenetic analysis of peripheral lymphocytes and lipid peroxidation in plasma

The clastogenic activity of paracetamol (PC) was assayed on a group of 11 healthy volunteers. PC was administered in the form of tablets 3 x 1000 mg in the course of 8 h. Blood samples were taken 0, 24, 72 and 168 h after the first application of the drug. Each blood sample was used for the cytogenetic analysis of peripheral lymphocytes, for the measuring of the level of lipid peroxidation (LPO) and ascorbemia in plasma. After PC administration the frequency of aberrant cells (AB.C.) was increased to 2.77% AB.C. after 24 h vs. 1.68% at 0 h, and breaks per cell (B/C) to 0.0295 vs. 0.0182, respectively. If PC was applied simultaneously with ascorbic acid (AA), also in a dose of 3 x 1000 mg, an increased frequency of AB.C. was observed only after 72 h, of B/C after both 24 h and 72 h. No increase in LPO as determined by the thiobarbituric acid assay was seen after PC administration (1.02-1.10 nmole malondialdehyde (MDA)/ml plasma). The LPO level was increased 72 h after the simultaneous application of PC and AA (1.26 nmole MDA/ml). No effect of AA in terms of a decreased PC clastogenicity was observed.