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Inflammation and oxidative stress in carcinogenesis
1Department of Carcinogenesis, Swiss Institute for Experimental Cancer Research, Epalinges/Lausanne.
Cancer Cells (Cold Spring Harbor, N.Y. : 1989)
|January 1, 1991
Summary
Oxidants contribute to cancer by causing DNA damage and promoting cell growth. Cellular antioxidant defenses modulate this growth promotion, with optimal effects occurring when cells are protected from toxicity but retain an oxidant signal.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Oxidants are endogenously generated in mammals through various pathways.
- Oxidative stress from inflammatory cells and clastogenic factors can induce DNA mutations and chromosomal aberrations.
Purpose of the Study:
- To investigate the role of oxidants in carcinogenesis.
- To explore how oxidants influence cell growth and proto-oncogene expression.
Main Methods:
- Analysis of oxidant-induced DNA damage (mutations, chromosomal aberrations).
- Investigation of signaling pathways activated by oxidants, including kinase activation and poly ADP-ribosylation.
- Assessment of the impact of cellular antioxidant defenses on oxidant-mediated cell growth.
Main Results:
- Oxidants can act as carcinogens, contributing to malignant transformation.
- Oxidant-induced DNA damage can affect proto-oncogenes and tumor suppressor genes.
- Oxidants promote cell growth by activating kinases and inducing poly ADP-ribosylation, participating in c-fos proto-oncogene induction.
Conclusions:
- Cellular antioxidant defenses critically modulate oxidant-driven cell growth.
- Maximal growth promotion occurs under conditions balancing oxidant toxicity and signaling for growth-competence gene induction.