Phenobarbitone-induced ploidy changes in liver occur independently of p53

Liver polyploidisation, characterised by accumulation of tetraploid and oct aploid cells, is found with increasing age and after administration of vari ous drugs. The significance and mechanisms controlling polyploidisation are not understood but p53 is a candidate gene to be involved. We have investi gated the effect of p53 on sodium phenobarbitone (PB)-induced liver prolife ration and polyploidisation. Using p53 wild type (+/+), heterozygous (+/-) and homozygous (-/-) C57BL/6J mice, we measured ploidy and proliferation (B rdU incorporation) after 21 days oral administration of PB. Administration of PB caused a striking ploidy change compared with untreated controls, wit h an increase in 8n cells, and no difference noted comparing the p53 genoty pes. BrdU positivity also increased significantly compared with controls, w ith the increase in BrdU positivity occurring in 8n cells. Our results conf irm that PB is a hepatic mitogen that causes liver polyploidisation with a striking increase in 8n cells within the liver. p53 status does not appear to have any effect on this PB-induced ploidy change. (C) 2001 Elsevier Scie nce Ireland Ltd. All rights reserved.