Evaluation of the ability of paracetamol to produce chromosome aberrations in man.
The ability of paracetamol to induce structural chromosome aberrations in human peripheral blood lymphocytes in vivo was evaluated in volunteers who had been administered a single oral dose of 3 g paracetamol, in patients who had received 2 g of propacetamol by intravenous infusion every 6 h for at least 7 days, and in self-poisoned patients who, for suicidal reasons, had ingested more than 15 g paracetamol. In addition to the in vivo observations, the effectiveness of paracetamol to interfere with fusorial microtubule polymerisation was assayed in vitro in order to detect a possible effect of paracetamol on the distribution of chromosomes during cell division. The negative results obtained in all those assays strongly suggest that paracetamol has no mutagenic properties in human. There was, indeed, no significant difference in the percentage of abnormal cells before and after application of paracetamol in volunteers (0.2% before ingestion of 3 g paracetamol, 0.12% after 24 h, 0.04% after 72 h and 0.04% after 168 h) and in patients (0.5% of abnormal cells before treatment versus 0.44% after intravenous infusion of a total of 28 g paracetamol). Moreover, the yield of abnormal cells was not modified in self-poisoned persons (0.24%), in spite of an important decrease in the mitotic index of the PHA stimulated lymphocytes. In the in vitro assay, no inhibition of microtubule polymerisation was detected with concentrations of 2.5, 5 and 10 mM paracetamol.
Hantson
P
P
Department of Intensive Care, Cliniques Universitaires St-Luc, Brussels, Belgium. hantson@rean.ucl.ac.be
de Saint-Georges
L
L
Mahieu
P
P
Léonard
E D
ED
Crutzen-Fayt
M C
MC
Léonard
A
A
D000082:Acetaminophen / Q000633:toxicity*; D000293:Adolescent; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000633:toxicity*; D002869:Chromosome Aberrations; D005260:Female; D006801:Humans; D008297:Male; D008870:Microtubules / Q000187:drug effects
D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen