Chronic infections and inflammatory processes as cancer risk factors: possible role of nitric oxide in carcinogenesis

Our plain-English summary of Chronic infections and inflammatory processes as cancer risk factors: possible role of nitric oxide in carcinogenesis, by H. Ohshima, H. Bartsch (Mutation Research, 1994).

The study

• Authors: H. Ohshima, H. Bartsch
• Journal: Mutation Research
• Published: 1994;305(2):253-64
• Type of article: Review
• Cited by: 868 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Infection by bacteria, parasites or viruses and tissue inflammation such as gastritis, hepatitis and colitis are recognized risk factors for human cancers at various sites. Nitric oxide (NO) and other oxygen radicals produced in infected and inflamed tissues could contribute to the process of carcinogenesis by different mechanisms, which are discussed on the basis of authors' studies on liver fluke infection and cholangiocarcinoma development. A similar mechanism could apply to other suspected and known cancer-causing agents including Helicobacter pylori infection (stomach cancer) or asbestos exposure (lung mesothelioma). Studies on the type of tissue and DNA damage produced by NO and by other reactive oxygen species are shedding new light on the molecular mechanisms by which chronic inflammatory processes may initiate or enhance carcinogenesis in humans.

In plain English

This 1994 article was a review, not a new study. The authors, at the International Agency for Research on Cancer in Lyon, France, reviewed work from their own and other laboratories on whether nitric oxide, a molecule made in infected and inflamed tissue, might contribute to cancer. They described possible routes: forming cancer-causing nitrosamines, damaging DNA, and injuring tissue. Much of the review drew on the authors' earlier work on liver fluke infection and bile duct cancer (cholangiocarcinoma). In one cited Thai study, people positive for liver fluke antibodies excreted significantly more N-nitrosoproline after swallowing proline than people who were negative, a test of the body's own capacity to form nitrosamines. Asbestos appeared only briefly. A table listed particles such as asbestos and silica dust as a risk factor, with the lung as the cancer site. The abstract suggested a similar mechanism could apply to asbestos exposure, which it linked to "lung mesothelioma". The review presented no asbestos data. The authors concluded that nitric oxide produced at high levels over long periods could damage DNA, leading to mutations and cancer. They noted this had not yet been shown in inflamed cells and tissues.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of laboratory, animal and human studies, including the authors' own earlier work
• Who was studied: No single study population. The review covered cell-culture, rat and hamster experiments and human studies. Many concerned people in north-east Thailand infested with liver flukes.
• Exposure: Nitric oxide and related reactive species produced during chronic infection and inflammation. Asbestos and silica dust were listed only in a table, as particles linked to cancer at the lung site.
• Main results:
  • In the authors' earlier cell-free macrophage work, activating macrophages with both LPS and interferon-gamma raised their nitrosation activity by a factor of 500-600 compared with non-activated macrophages.
  • In rats given P. acnes and then LPS, nitrosated product (NTCA) in urine was about 5-, 10- and 8-fold greater (for intravenous, intraperitoneal and oral dosing of the precursor) than in rats not given P. acnes with LPS.
  • In a cited earlier study (Srivatanakul et al., 1991), after proline ingestion, subjects positive for O. viverrini antibody excreted significantly more N-nitrosoproline (p less than 0.01; mean 12.3 plus or minus 18.7 micrograms per 12 hours, n = 23) than negative subjects (3.5 plus or minus 3.2, n = 18). The authors took this to indicate elevated endogenous nitrosation potential in infested subjects.
  • In unpublished (in preparation) work on hamsters infested with O. viverrini, an inducible form of NO synthase was found in macrophages and eosinophils in the inflamed area around infested bile ducts.
• The authors' conclusion: The authors concluded that if nitric oxide is produced for a long time at high concentrations in chronically infected or inflamed tissue, the excess could damage DNA, leading to gene mutations and cancer.
• Limitations the authors state:
  • The authors stated it had not yet been shown that nitric oxide made by mammalian cells causes DNA deamination and point mutations in inflamed cells and tissues.
  • The authors stated that the role of nitric oxide, and the effect of blocking NO synthase, in cancer development needed further study.

Topics

Medical terms in this study, explained in our Lexicon: Carcinogenesis, Inflammation, Stomach Cancer, Asbestos Exposure, Mesothelioma, Reactive Oxygen Species (ROS).

Related studies

• Intrapleural interleukin-2 induces nitric oxide production in pleural effusions from malignant mesothelioma: a possible mechanism of interleukin-2-mediated cytotoxicity? — C. Porta, V. Rizzo, et al. (2002)
• The role of iNOS-mediated DNA damage in infection- and asbestos-induced carcinogenesis — Y. Hiraku, S. Kawanishi, et al. (2010)
• Mechanisms of asbestos-induced nitric oxide production by rat alveolar macrophages in inhalation and in vitro models — T.R. Quinlan, K.A. BeruBe, et al. (1998)
• Dual role of inducible nitric oxide synthase in acute asbestos-induced lung injury — M. Dörger, A.M. Allmeling, et al. (2002)
• Role of nitric oxide in the progression of pneumoconiosis — V. Castranova (2004)
• Beyond foreign-body-induced carcinogenesis: impact of reactive oxygen species derived from inflammatory cells in tumorigenic conversion and tumor progression — F. Okada (2007)

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