Alkylation of DNA in rat tissues following administration of streptozotocin

Richard A. Bennett, Anthony E. Pegg

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148 Scopus citations

Abstract

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 N-methyl-N-nitrosou-rea, 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 N-methyl-N-nitrosourea which produced 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-N-nitrosourea. This methylation of renal DNA may account for the ability of streptozotocin to induce renal tumors. Streptozotocin produced significant methylation of pancreatic DNA which, if concentrated in the β-cells, may account for their destruction. Pretreatment with nicotinamide reduced the extent of methylation of pancreatic DNA but did not affect the methylation in the liver or kidney. Methylation of β-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.

Original languageEnglish (US)
Pages (from-to)2786-2790
Number of pages5
JournalCancer Research
Volume41
Issue number7
StatePublished - Jul 1 1981

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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