Nucleotide Excision Repair of Actively Transcribed Versus Nontranscribed DNA in Rat Hepatocytes: Effect of Age and Dietary Restriction

The ability of primary cultures of rat hepatocytes to remove cyclobutane pyrimidine dimers (CPDs) from DNA fragments containing the transcriptionally active albumin gene and the transcriptionally inactive embryonic myosin heavy chain (MHCemb) andH-rasfragments as well as the genome overall was measured. At all UV doses studied, more CPDs were observed in the three DNA fragments and the genome overall in hepatocytes isolated from old (24-month-old) rats fedad libitumthan in young (6-month-old) rats fedad libitumor old rats fed a calorie-restricted diet. The cultured hepatocytes preferentially removed CPDs from the albumin fragment compared to the genome overall or the MHCembandH-rasfragments. The rate of repair (12 h after UV irradiation) of the albumin fragment was approximately 40% less in hepatocytes isolated from old rats than from young rats; this was due to a decrease in repair of the transcribed strand of this fragment, and dietary restriction prevented this decrease. The extent of repair (24 h after UV irradiation) of the MHCembandH-rasfragments as well as the genome overall was reduced approximately 40% with age, and this decrease was reversed by dietary restriction.