Abstract
Treatment of BDF1 mice with AdR/dCf combinations (daily x5) leads to acute hepatic dysfunction with accumulative dose related hepatocellular necrosis (Paine et al Cancer Treat. Rep. 65:281-266, 1971). In vivo inhibition of liver S-adenosyl-homocysteine (SAH) hydrolase by AdR is implicated since liver SAH levels increase dramatically following treatment. S-adenosylmethionine (SAM) levels also increase and the SAM:SAH ratios drop from control values of 15 to <1 (Renshaw & Harrap, in Purine Metabolism in Man, Vol. 165B, Plenum Press, pp 363-366, 1984). Further investigations have revealed that while SAH and SAM levels and their ratios normalise following the first 2 days treatment, recovery does not occur thereafter. These data indicate a correlation between the duration of depression of SAM:SAH ratios and the manifestation of hepatocellular necrosis. In addition we have obtained evidence of in vivo inhibition of MT reactions as a result of reduced SAM:SAH ratios: both plasma and urinary creatinine levels are significantly reduced (eg, 23% control urinary creatinine levels by day 5) reflecting inhibition of liver guanidinioacetate MT. Plasma:urinary creatinine ratios do not alter indicating a lack of kidney toxicity in mice. Treated animals also excrete significantly less pseudouridine (<30% from day 2) which may reflect a biochemical lesion at the level of tRNA post-transcriptional modification.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
