Related Experiment Video

Updated: Aug 14, 2026

A General Method for Detecting Nitrosamide Formation in the In Vitro Metabolism of Nitrosamines by Cytochrome P450s
07:38

A General Method for Detecting Nitrosamide Formation in the In Vitro Metabolism of Nitrosamines by Cytochrome P450s

Published on: September 25, 2017

Alkylation of DNA related to organ-specific carcinogenesis by N-nitroso compounds

W Lijinsky1

  • 1National Cancer Institute, Frederick Cancer Research Facility, Bionetics Research Inc., MD.

IARC Scientific Publications
|January 1, 1991
PubMed

Insights

DNA alkylation by carcinogens like N-nitroso compounds showed similar patterns in target and non-target organs. Other carcinogen reactions, not DNA alkylation, are key to tumor development.

Area of Science:

  • Toxicology
  • Carcinogenesis
  • Molecular Biology

Background:

  • N-nitroso compounds are known carcinogens that alkylate DNA.
  • Understanding the relationship between DNA alkylation patterns and tumor formation is crucial for cancer research.

Purpose of the Study:

  • To investigate DNA alkylation by methylating and ethylating carcinogens in various organs of rats and Syrian hamsters.
  • To compare DNA alkylation patterns in target versus non-target organs and correlate them with carcinogenicity.

Main Methods:

  • Administration of methylating and ethylating carcinogens (including N-nitroso compounds) to rodents.
  • Isolation and hydrolysis of DNA from various organs.
  • Quantification of methyl- and ethylguanines using high-performance liquid chromatography (HPLC) and fluorescence detection.
  • Use of radiolabeled and deuterium-labeled carcinogens to trace reactions.

Main Results:

  • Methylation of DNA was more extensive than ethylation, regardless of the carcinogen's tumor-inducing potency.
  • Similar DNA alkylation patterns were observed in both target and non-target organs.
  • Minor differences in DNA methylation were noted between male and female rat livers, despite sex-specific tumor induction.
  • Deuterium labeling of a carcinogen did not significantly alter DNA alkylation but increased its potency, suggesting non-alkylation mechanisms.

Conclusions:

  • DNA alkylation patterns do not fully explain the organ specificity or potency of carcinogens.
  • Reactions of the carcinogen other than direct DNA alkylation play a significant role in tumor initiation.

More Related Videos

Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling09:33

Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling

Published on: March 20, 2018

Quantification of three DNA Lesions by Mass Spectrometry and Assessment of Their Levels in Tissues of Mice Exposed to Ambient Fine Particulate Matter12:15

Quantification of three DNA Lesions by Mass Spectrometry and Assessment of Their Levels in Tissues of Mice Exposed to Ambient Fine Particulate Matter

Published on: May 29, 2019

Related Concept Videos

Carboxylic Acids to Methylesters: Alkylation using Diazomethane01:33

Carboxylic Acids to Methylesters: Alkylation using Diazomethane

Carboxylic acids react with diazomethane in an ether solvent via alkylation at the carboxylate oxygen atom to give methyl esters of the corresponding acid with excellent yields.
2° Amines to N-Nitrosamines: Reaction with NaNO201:20

2° Amines to N-Nitrosamines: Reaction with NaNO2

Secondary amines react with nitrous acid to form N-nitrosamines, as depicted in Figure 1. Nitrous acid, a weak and unstable acid, is formed in situ from an aqueous solution of sodium nitrite and strong acids, such as hydrochloric acid or sulfuric acid, in cold conditions. In the presence of an acid, the nitrous acid gets protonated. The subsequent loss of water results in the formation of the electrophile known as nitrosonium ion.
Nitrosation of Enols01:19

Nitrosation of Enols

The nitrosation reaction is one of the methods of preparing 1,2-diketones. The enol tautomer of the starting ketone reacts with sodium nitrite in hydrochloric acid, generating the 1,2-diketone after hydrolysis.
Mutagenicity and Carcinogenicity01:25

Mutagenicity and Carcinogenicity

Mutagenicity and carcinogenicity refer to the ability of drugs to cause genetic defects and induce cancer, respectively. The International Agency for Research on Cancer (IARC) classifies agents into four groups based on their carcinogenic potential. Group 1 agents are known human carcinogens; group 2A agents are probably carcinogenic to humans; group 3 agents lack data to support their role in carcinogenesis; and group 4 includes agents for which data support that they are not likely to be...
Bioactivation and Tissue Toxicity01:25

Bioactivation and Tissue Toxicity

Bioactivation is a metabolic process that transforms less reactive substances into highly reactive metabolites, initiating tissue toxicity. This transformation can lead to various toxic effects, including carcinogenesis and teratogenesis. Reactive metabolites are classified into two main types: electrophiles and free radicals.Electrophiles are electron-deficient species and are produced primarily by the enzyme cytochrome P-450 during the metabolism of compounds containing carbon, nitrogen, or...
Spontaneous and Induced Mutations01:30

Spontaneous and Induced Mutations

Spontaneous mutations arise infrequently during DNA replication due to errors in the process. A key factor behind these errors is tautomeric shifts in nitrogenous bases, where bases transition from keto to enol forms or amino to imino forms. This shift can alter base-pairing rules, leading to mutations. Additionally, reactive oxygen species (ROS) arising from aerobic metabolism can damage DNA, resulting in depurination (loss of a purine base) or depyrimidination (loss of a pyrimidine base).