Mutagenicity studies on paracetamol in human volunteers. II. Unscheduled DNA synthesis and micronucleus test.
The possible genotoxic effect of paracetamol (PC) was studied in 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 and buccal mucosa cells were taken 0, 24, 72 and 168 h after the first administration of the drug. Each blood sample was used for the termination of the unscheduled DNA synthesis (UDS) in peripheral lymphocytes and ascorbemia in plasma. Buccal mucosa cells were analysed for micronuclei. After PC administration the level of UDS induced by MNNG was decreased to T/C = 4.11 +/- 0.56 after 24 h vs. T/C = 5.02 +/- 0.47 (p less than 0.01) at 0 h. The frequency of micronucleated cells in the buccal mucosa was increased after 72 h to 0.38 +/- 0.07% vs. 0.19 +/- 0.06% (p less than 0.01) before PC administration. If PC was administered simultaneously with ascorbic acid (AA), also in a dose of 3 X 1000 mg, a decreased level of UDS was observed after 24, 72 and 168 h and the increased number of micronuclei was qualitatively the same as the PC alone: 0.38 +/- 0.09% after 72 h vs. 0.20 +/- 0.05% at 0 h AA did not decrease the genotoxic effect of PC, but prolonged the influence of PC on UDS.
Topinka
J
J
Psychiatric Research Institute, Prague, Czechoslovakia.
Srám
R J
RJ
Sirinjan
G
G
Kocisová
J
J
Binková
B
B
Fojtíková
I
I
D000082:Acetaminophen / Q000633:toxicity*; D000328:Adult; D001205:Ascorbic Acid / Q000494:pharmacology; D004260:DNA Repair / Q000187:drug effects*; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D008769:Methylnitronitrosoguanidine / Q000633:toxicity; D015162:Micronucleus Tests; D009061:Mouth Mucosa / Q000187:drug effects; D009152:Mutagenicity Tests; D009153:Mutagens
D009153:Mutagens; D008769:Methylnitronitrosoguanidine; D000082:Acetaminophen; D001205:Ascorbic Acid