Genotoxic effects of paracetamol in V79 Chinese hamster cells.
Paracetamol was studied for possible genotoxic effects in V79 Chinese hamster cells. Paracetamol (0.5 mM for 30 min) reduced the rate of DNA synthesis in exponentially growing V79 cells to about 50% of control. A further decrease in the DNA synthesis was seen during the first 30 min after termination of paracetamol exposure. Paracetamol (3 and 10 mM for 2 h) caused a small increase in DNA single-strand breaks, as measured by the alkaline elution technique. After 16 h elution, the amount of DNA retained on the filters was 79 and 70% of controls in cells treated with 3 and 10 mM paracetamol respectively. No indication of DNA damage was seen in measuring the effect of paracetamol (0.25-10 mM for 2 h) on unscheduled DNA synthesis in growth-arrested cultures of V79 cells. At the highest concentrations (3 and 10 mM paracetamol), decreased unscheduled DNA synthesis was observed. Also UV-induced DNA-repair synthesis was inhibited by 3 and 10 mM paracetamol. DNA-repair synthesis was, however, inhibited at a much higher concentration than that inhibiting replicative DNA synthesis. The number of sister-chromatid exchanges (SCE) increased in a dose-dependent manner on 2 h exposure to paracetamol from 1 mM to 10 mM. At the highest dose tested (10 mM), the number of SCE increased to 3 times the control value. Co-culturing the V79 cells with freshly isolated mouse hepatocytes had no further effect on the paracetamol induced sister-chromatid exchanges. The present study indicates that paracetamol may cause DNA damage in V79 cells without any external metabolic activation system added.
Hongslo
J K
JK
Department of Toxicology, National Institute of Public Health, Oslo, Norway.
Christensen
T
T
Brunborg
G
G
Bjørnstad
C
C
Holme
J A
JA
D000082:Acetaminophen / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects*; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008168:Lung; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009152:Mutagenicity Tests; D012854:Sister Chromatid Exchange / Q000187:drug effects*
D000082:Acetaminophen