Alkylation of DMA in Rat Tissues following Administration of Streptozotocin1

نویسندگان

  • Richard A. Bennett
  • Anthony E. Pegg
چکیده

Streptozotocin, an antibiotic widely used for induction of diabetes in experimental animals and for the treatment of pancreatic neoplasms, was shown to be a potent methylating agent reacting with DNA in vitro to form methylated purines. The reaction was similar in extent and relative proportions of methylation products to that produced by /V-methyl-N-nitrosourea, the aglycone of Streptozotocin. When Streptozotocin was administered to rats by i.v. injection, DNA was methylated with the formation of 7-methylguanine, O6-methylguanine, 3-methyladenine, and 7-methyladenine in liver, kidney, intestine, and pancreas. In contrast to A/-methyl-A/-nitrosourea which pro duced approximately equal amounts of methylation in DNA of liver, brain, and kidney, Streptozotocin caused virtually no methylation in brain DNA; but, both liver and kidney DNA were alkylated to a greater extent than with N-methyl-A/-nitrosourea. This methylation of renal DNA may account for the ability of Streptozotocin to induce renal tumors. Streptozotocin pro duced significant methylation of pancreatic DNA which, if con centrated in the /S-cells, may account for their destruction. Pretreatment with nicotinamide reduced the extent of methyl ation of pancreatic DNA but did not affect the methylation in the liver or kidney. Methylation of /3-cell DNA in the pancreas may lead to the initiation of tumors if the extent of alkylation is not so great that cell death occurs.

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تاریخ انتشار 2004