MOLECULAR MECHANISMS ASSOCIATED WITH MARKERS OF HEPATOCARCINOGENICITY DURING A 14 DAY DIETARY STUDY IN MALE FISCHER RAT

To investigate the molecular mechanisms associated with initial dose-related events that are linked to the development of liver tumours: liver growth; cell proliferation; changes in histopathology such as hypertrophy We selected dose levels of phenobarbital to give a carcinogenic (1000ppm) and two non-carcinogenic doses (50 and 500ppm). This also gave two doses that increased liver weights (500 and 1000ppm) and one that did not (50ppm). Alterations to liver growth and proliferation are complete after 14 days of dietary treatment and so we chose intermediate time points of 1,3 7 and 14 days of treatement. Small sections of the left lateral lobe of the liver were processed to give three biological replicates selected from the 5 treated animals in each group, total RNA purified and mRNA levels measured using Affymetrix Rat Genome 230 v2 microarrays. In addition we also measured a braod range of standard histopathological, clincal chemsitry and metabolomic endpoints.