The administration to male rats of the hepatocarcinogen 2-acetylaminofluorene (AAF) results in significant increases in liver transfer RNA (tRNA)-methylating enzyme activity and changes in the specificity of these enzymes. These effects are apparent within 5 days and persist throughout the AAF treatment period. Comparison of tRNA-methylating enzyme activity in liver, colon, and spleen of these animals showed that the effects of this carcinogen on the tRNA methyltransferases of various organs are not uniform. When AAF was given for 3 weeks, the activity of liver tRNA methylases was increased as much as 100%, in some cases; the activity of spleen and colon enzymes did not differ significantly from that of controls. Since female rats are relatively resistant to hepatocarcinogenesis by AAF, the effects of AAF administration on liver tRNA methylase activity in females were also measured. AAF administration for 5 days resulted in only small, transient increases in liver tRNA methylase activity and, after 3 weeks of AAF ingestion, the activity levels of liver tRNA methylases of female rats were the same as those of untreated controls. The organ and sex specificity of AAF-induced changes in methyltransferase activity thus seem to parallel the organ and sex specificity of AAF as a carcinogen.
In order to see whether the increases found in liver tRNA methylase activity in the male rats might be caused by endogenous polyamines, the concentrations of putrescine, spermidine, and spermine in the livers of control and AAF-treated animals were measured. No significant differences between liver polyamine levels in control and treated animals were found. The selective elevation of liver tRNA methylase activity seen in response to AAF ingestion thus appeared not to be directly related to changes in the polyamine content of the tissues.
In view of the observations by several groups of investigators that the metabolism of AAF is not identical in all tissues and is not the same in male and female rat liver, it seems possible that the sex-specific and organ-selective effects of AAF on tRNA-methylating enzymes are caused at least in part by differences in the derivatives of this carcinogen in the different tissues.
This research was supported in part by USPHS Grants HL09011, CA08748, and F32-CA 05494 and by NIH Grant CA 14906 from the National Large Bowel Cancer Program.