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Free-radical processes in multistage carcinogenesis
1Department of Radiation Oncology, Columbia University New York, N.Y. 10032.
Abstract:
Rodent and human cells in culture, transformed in vitro by radiation or chemicals into malignant cells, afford us the opportunity to probe into early and late events in the neoplastic process at a cellular and molecular level. Transformation can be regarded as an abnormal expression of cellular genes. The initiating agents disrupt the integrity of the genetic apparatus altering DNA in ways that result in the activation of cellular transforming genes (oncogenes) during some stage of the neoplastic process. Events associated with initiation and promotion may overlap to some degree, but in order for them to occur, cellular permissive conditions prevail. Permissive and potentiating factors include free radicals, and thyroid hormone, and inadequate antioxidants. Protective factors which suppress the carcinogenic process include enzymatic and dietary antioxidants. These are constitutive under normal circumstances and can be induced under conditions of oxidative stress produced by a wide range of carcinogens.
Insights
Cancer research uses cell cultures to study neoplastic transformation, focusing on gene activation and the roles of oxidative stress, hormones, and antioxidants in cancer development.
Area of Science:
- Cellular and molecular biology
- Cancer research
- Carcinogenesis
Background:
- Malignant cell transformation in vitro provides a model to study cancer development.
- Cancer initiation involves genetic damage and the activation of oncogenes.
- Cellular conditions and external factors influence neoplastic progression.
Purpose of the Study:
- To investigate early and late events in the neoplastic process.
- To understand the role of gene expression in transformation.
- To identify factors influencing cancer initiation and promotion.
Main Methods:
- In vitro transformation of rodent and human cells using radiation or chemicals.
- Analysis of cellular and molecular events during neoplastic progression.
- Examination of genetic alterations and oncogene activation.
Main Results:
- Transformation involves abnormal cellular gene expression.
- Initiating agents damage DNA, leading to oncogene activation.
- Oxidative stress, thyroid hormone, and inadequate antioxidants promote cancer.
- Enzymatic and dietary antioxidants protect against carcinogens.
Conclusions:
- Cell transformation is a complex process involving genetic changes and environmental factors.
- Antioxidants play a crucial role in suppressing carcinogenesis.
- Understanding these mechanisms can inform cancer prevention strategies.