Effect of hypoxia on hepatic DNA methylation and tRNA methyltransferase in rat: Similarities to effects of methyl-deficient diets

✍ Scribed by Rajender K. Chawla; Walter H. Watson; Dean P. Jones

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 836 KB
• Volume: 61
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/(sici)1097-4644(19960401)61:1<72::aid-jcb9>3.0.co;2-#

✦ Synopsis

Young rats were maintained in a 10% oxygen atmosphere for 2 , 6 , and 10 days and administered normal rat chow and water ad libitum. Thereafter, their hepatic S-adenosyl-L-methionine (AdoMet) and activity and mRNA levels of AdoMet synthetase were assayed. AdoMet levels decreased by 45% after 10 days; hepatic AdoMet synthetase also declined by -40%. In rats with low hepatic AdoMet, the mRNA level of AdoMet synthetase also declined by up to 80%. No significant change in AdoMet or AdoMet synthetase was noted in pair-fed normoxic rats. DNA hypomethylation was determined in terms of incorporation of [3H]methyl of AdoMet incorporated at unmethylated sites in DNA in reactions mediated by methylases Hpall and Sssl. As compared to the normal hepatic DNA, [3H]methyl group incorporation in the 1 O-day hypoxic DNA was almost double in the Hpall-mediated reaction and -1 O-fold in the Sssl-mediated reaction. Hepatic tRNA methyltransferase activity doubled after 10 days of hypoxia. However, hypoxic rats showed no detectable mRNA transcripts for c-rnyc and c-fos oncogenes on Northern blot analysis. These observations show that because of subnormal activity of AdoMet synthetase, hypoxic liver is depleted of AdoMet, even when the animals are administered a complete diet. However, unlike rats on chronic lipotrope-deficient diets, hypoxic rats on a complete diet show no aberrant expression of oncogenes.