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Genotoxicity, carcinogenicity and acid-suppressing medications
R E Powers1, G P Lawton, I M Modlin
1Department of Surgery, Yale University School of Medicine, New Haven, CT 06520-8062, USA.
Abstract:
With the availability of increasingly potent acid-suppressing medications, questions continue to rise concerning the safety of these compounds in regards to carcinogenetic potential. In this review, we examine current concepts and procedures relating to genotoxicity, the potential for a chemical agent to interact with and alter the genomic information of the cell, and carcinogenesis. A description and discussion of commonly utilized techniques for the determination of (a) in vitro mutagenicity, (b) in vitro and in vivo DNA damage and repair, (c) in vitro and in vivo chromosomal damage and (d) chronically dosed animal tumorigenesis development is presented. Observations from these procedures as they have been applied to a review of the safety of acid-suppressing medications will be discussed. An evaluation of reports relating to potential genotoxic and carcinogenic hazards of therapeutically relevant acid-suppressing medications (cimetidine, ranitidine, omeprazole) is presented. Information related to the effect of prolonged administration of acid-suppressing medications, alterations of serum gastrin levels, and the potential for tumor promotion is discussed.
Insights
This review explores the carcinogenic potential of acid-suppressing medications. It examines genotoxicity and carcinogenesis, assessing the safety of common drugs like omeprazole.
Area of Science:
- Pharmacology
- Toxicology
- Genetics
Background:
- Increasingly potent acid-suppressing medications raise safety concerns regarding carcinogenicity.
- Genotoxicity, the alteration of cellular genomic information by chemical agents, is a key area of investigation.
- Carcinogenesis, the process by which normal cells become cancerous, is evaluated in relation to these drugs.
Purpose of the Study:
- To review current concepts and procedures for assessing genotoxicity and carcinogenesis.
- To evaluate the safety of therapeutically relevant acid-suppressing medications concerning their carcinogenic potential.
- To discuss the effects of prolonged drug administration, including serum gastrin level alterations and tumor promotion.
Main Methods:
- Description and discussion of techniques for determining in vitro mutagenicity.
- Assessment of in vitro and in vivo DNA damage and repair mechanisms.
- Evaluation of in vitro and in vivo chromosomal damage.
- Analysis of chronically dosed animal tumorigenesis development.
Main Results:
- Observations from applied genotoxicity and carcinogenesis procedures are discussed.
- Evaluation of reports on potential genotoxic and carcinogenic hazards of cimetidine, ranitidine, and omeprazole.
- Information on prolonged administration effects, serum gastrin alterations, and tumor promotion potential is presented.
Conclusions:
- The review provides an evaluation of the genotoxic and carcinogenic risks associated with commonly used acid-suppressing medications.
- Understanding these risks is crucial for informed clinical practice and patient safety.
- Further research may be warranted to fully elucidate long-term safety profiles.