Increased frequency of sister-chromatid exchange and chromatid breaks in lymphocytes after treatment of human volunteers with therapeutic doses of paracetamol.
Paracetamol was given to 10 healthy human volunteers in 3 doses of 1 g each during a period of 8 h. Blood samples for lymphocyte cultures were taken before and 24 h after paracetamol administration. A small but significant increase was found in the frequency of sister-chromatid exchanges (SCE) after intake of paracetamol (0.187 +/- 0.030 per chromosome before and 0.208 +/- 0.024 per chromosome after). After exposure the mean frequency of chromatid breaks per 100 cells was significantly increased (2.16 +/- 1.33 versus 0.33 +/- 0.50 before exposure). Exposure of human lymphocytes in vitro showed that concentrations of paracetamol above 0.1 mM induced inhibition of replicative DNA synthesis. Increased SCE was found in lymphocytes exposed to 1-10 mM paracetamol for 2 h. Furthermore, 0.75-1.5 mM paracetamol exposure for 24 h increased the frequency of chromatid and chromosome breaks in the lymphocytes. The paracetamol-induced SCE and chromosome aberrations may be secondary effects of paracetamol-induced inhibition of DNA synthesis or due to covalent binding of paracetamol metabolite(s) to DNA.
Hongslo
J K
JK
Department of Environmental Medicine, National Institute of Public Health, Oslo, Norway.
Brøgger
A
A
Bjørge
C
C
Holme
J A
JA
D000082:Acetaminophen / Q000009:adverse effects*; D002478:Cells, Cultured; D002875:Chromosomes / Q000187:drug effects; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000648:ultrastructure; D008297:Male; D009153:Mutagens; D012854:Sister Chromatid Exchange / Q000187:drug effects*
D009153:Mutagens; D000082:Acetaminophen