Related Experiment Videos
Inhibitors of endogenous nitrosation. Mechanisms and implications in human cancer prevention
H Bartsch1, H Ohshima, B Pignatelli
1International Agency for Research on Cancer, Lyon, France.
Abstract:
Although the proof that N-nitroso compounds (NOC), a versatile class of carcinogens in animals, are also carcinogenic in man is lacking, humans are exposed through ingestion or inhalation to preformed NOC in the environment and through the endogenous nitrosation of amino precursors in the body. Activated macrophages can synthesize nitrate, nitrite and nitrosating agents that can form NOC. A number of bacterial strains isolated from human infections can produce NOC enzymatically from precursors at neutral pH. As a consequence endogenous nitrosation may occur at various sites of the body such as the oral cavity, stomach, urinary bladder, lungs, and at other sites of infection or inflammation. Since the demonstration by Mirvish et al. (1972) showing that ascorbate can reduce tumor formation in animals following feeding of nitrite plus amine, numerous substances to which humans are exposed have been identified and shown to inhibit formation of NOC in vitro, in animal models and in humans. Such inhibitors of nitrosation include vitamins C and E, phenolic compounds, and complex mixtures such as fruit and vegetable juices or other plant extracts. Nitrosation inhibitors normally destroy the nitrosating agents and thus act as competitors for the amino compound that serves as substrate for the nitrosating species. Independently, epidemiological studies have already established that fresh fruits and vegetables that are sources of vitamin C, other vitamins and polyphenols have a protective effect against cancers at various sites and in particular gastric cancer. Although the evidence that endogenously formed NOC are involved in human cancers is far from conclusive, it is suggestive and justifies preventive measures for reducing exposure to NOC. This article briefly reviews (i) the chemistry of NOC formation and inhibition, (ii) the studies in experimental animals which showed that inhibition of endogenous NOC synthesis leads to a reduction of toxic, mutagenic and carcinogenic effects, (iii) recent studies in humans where the degree of inhibition of endogenous NOC synthesis was directly quantified and lastly (iv) the contribution of nitrosation inhibitors to human cancer prevention.
Insights
Humans are exposed to N-nitroso compounds (NOC), potential carcinogens, through diet and internal processes. Inhibitors like vitamins and plant extracts can block NOC formation, suggesting a role in cancer prevention.
Area of Science:
- Toxicology
- Carcinogenesis
- Preventive Medicine
Background:
- N-nitroso compounds (NOC) are animal carcinogens, and humans are exposed via environment and endogenous formation.
- Endogenous nitrosation can occur in various body sites, influenced by factors like bacterial activity and inflammation.
- Ascorbate (vitamin C) and other inhibitors reduce NOC formation, as shown in animal studies.
Purpose of the Study:
- To review the chemistry of NOC formation and inhibition.
- To summarize animal studies on NOC synthesis inhibition and its effects.
- To discuss human studies quantifying endogenous NOC synthesis inhibition and its role in cancer prevention.
Main Methods:
- Review of chemical mechanisms of NOC formation and inhibition.
- Analysis of experimental animal studies investigating NOC synthesis inhibition.
- Examination of human studies measuring endogenous NOC synthesis inhibition.
- Evaluation of epidemiological data on cancer risk and dietary factors.
Main Results:
- Numerous inhibitors, including vitamins C and E, phenolics, and plant extracts, are identified.
- Inhibitors function by destroying nitrosating agents, competing with amino compounds.
- Animal studies demonstrate reduced toxicity, mutagenicity, and carcinogenicity with NOC synthesis inhibition.
- Human studies show direct quantification of endogenous NOC synthesis inhibition is possible.
Conclusions:
- While direct proof of human carcinogenicity of NOC is limited, suggestive evidence warrants preventive measures.
- Inhibitors of nitrosation, abundant in fruits and vegetables, show promise in cancer prevention strategies.
- Reducing exposure to NOC and promoting intake of inhibitors may lower cancer risk, particularly gastric cancer.