The effect of paracetamol on oxidative damage in human peripheral lymphocytes

Unscheduled DNA synthesis (UDSox) and lipid peroxidation (LPO) induced by non-enzymatic activation of molecular oxygen (Fe2+ +H2O2) were measured in human peripheral lymphocytes from healthy volunteers. The effect of paracetamol (PC) in a final concentration range of 0.05-10 mmole/l on these oxidative processes and on DNA repair induced by MNNG (UDSmut) was investigated. The level of induced LPO was measured by the thiobarbituric acid assay, UDSox and UDSmut were determined by scintillometric measurement of incorporated [methyl-3H]thymidine into damaged DNA. PC at concentrations lower than 1 mmole/l significantly potentiates the non-enzymatically induced LPO and UDSox with the maximum of the activation being around 0.1 mmole/l. In contrast, PC at concentrations higher than 1 mmole/l exhibits an inhibitory effect on both LPO and UDSox. On the other hand, concentrations higher than 1 mmole/l significantly suppressed DNA-repair synthesis induced by MNNG.