Alkylation of DNA in rat tissues following administration of streptozotocin

Richard A. Bennett, Anthony E. Pegg

Research output: Contribution to journalArticle

143 Citations (Scopus)

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

Fingerprint

Alkylation
Streptozocin
DNA Methylation
Kidney
DNA
Methylation
Methylnitrosourea
Liver
Pancreas
Purines
Niacinamide
Brain
Pancreatic Neoplasms
Intestines
Neoplasms
Cell Death
Anti-Bacterial Agents
Injections

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

@article{3d48b3f440224de38541ec83d812b08c,
title = "Alkylation of DNA in rat tissues following administration of streptozotocin",
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.",
author = "Bennett, {Richard A.} and Pegg, {Anthony E.}",
year = "1981",
month = "7",
day = "1",
language = "English (US)",
volume = "41",
pages = "2786--2790",
journal = "Cancer Research",
issn = "0008-5472",
number = "7",

}

Alkylation of DNA in rat tissues following administration of streptozotocin. / Bennett, Richard A.; Pegg, Anthony E.

In: Cancer Research, Vol. 41, No. 7, 01.07.1981, p. 2786-2790.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Alkylation of DNA in rat tissues following administration of streptozotocin

AU - Bennett, Richard A.

AU - Pegg, Anthony E.

PY - 1981/7/1

Y1 - 1981/7/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0019501634&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0019501634&partnerID=8YFLogxK

M3 - Article

C2 - 6454479

AN - SCOPUS:0019501634

VL - 41

SP - 2786

EP - 2790

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 7

ER -