The Role of Free Radicals and Dietary Antioxidants in Cellular and Molecular Carcinogenesis
Maryce M. Jacobs in Vitamins and Minerals in the Prevention and Treatment of Cancer, 2018
The dietary factors act as protectors by enhancing cellular free radical scavenging systems or modifying lipid peroxidation. The results support the notion that free radicals play an important role in carcinogenesis and that dietary factors can serve as cancer preventing agents. Studies in cell cultures have shown that transformation of cells by direct exposure to radiation or chemicals is associated with the activation of dominant transforming genes which specify many of the malignant traits of the cells. In recent years, increasing evidence has implicated free radical mechanisms in the initiation and promotion of malignant transformation in vivo and in vitro . The role of free radicals in the carcinogenic process can be inferred from the protective action of agents which attenuate free radical reactions at different stages of the oxidative process. However, their role in carcinogenesis can further be evaluated by exposing the cells to the direct action of ozone, an active form of ozone and a powerful oxidant.
Radiation Carcinogenesis: Tissue Culture Model
Kedar N. Prasad in Handbook of RADIOBIOLOGY, 2020
Radiation-induced neoplasms cannot be distinguished from those that occur spontaneously or that are induced by chemicals. The structural and functional changes in carcinogenesis may be similar irrespective of causative agents. Cancer cells result from accumulation of multiple genetic changes in normal dividing cells, which occur over a long period of time. The latent period (time interval between exposure to carcinogens and detection of cancer) of a neoplasm depends upon the experimental models. Three models are used to study radiation carcinogenesis: the tissue culture model, the animal model, and the human model. The latent period of cancer is about a few weeks in the tissue culture model, about a few months in the animal model, and several years in the human model. Each model will be discussed in a separate chapter.
Defining cancer
Ian Peate in Nursing & Health Survival Guide, 2014
The term cancer is used for diseases in which abnormal cells divide without control, and can invade other tissues; in essence, a disruption in the regulation of growth of healthy cells occurs. Cells proliferate without normal organisation or normal control; cellular function becomes distorted, this is called carcinogenesis. Cancer is a general term describing a group of related diseases. Every case of cancer is unique, with its own group of genetic changes and growth properties: it is essential to remember that the people who have cancer and their families are also unique. Cancer can be grouped into broader categories: Carcinoma, Sarcoma, Leukaemia, Lymphoma, and Central nervous system. The development of cancer is a complex process involving the disruption of the regulation of the growth of normal cells. Differentiation radically alters a cell's size, shape, membrane potential, metabolic activity and the cell's responsiveness to signals.
Cobalt and its compounds: update on genotoxic and carcinogenic activities
Published in Critical Reviews in Toxicology, 2018
D. Lison, S. van den Brule, G. Van Maele-Fabry
This article summarizes recent experimental and epidemiological data on the genotoxic and carcinogenic activities of cobalt compounds. Emphasis is on the respiratory system, but endogenous exposure from Co-containing alloys used in endoprostheses, and limited data on nanomaterials and oral exposures are also considered. Two groups of cobalt compounds are differentiated on the basis of their mechanisms of toxicity: (1) those essentially involving the solubilization of Co(II) ions, and (2) metallic materials for which both surface corrosion and release of Co(II) ions act in concert. For both groups, identified genotoxic and carcinogenic mechanisms are non-stochastic and thus expected to exhibit a threshold. Cobalt compounds should, therefore, be considered as genotoxic carcinogens with a practical threshold. Accumulating evidence indicates that chronic inhalation of cobalt compounds can induce respiratory tumors locally. No evidence of systemic carcinogenicity upon inhalation, oral or endogenous exposure is available. The scarce data available for Co-based nanosized materials does not allow deriving a specific mode of action or assessment for these species.
Biomarkers of carcinogenicity and their roles in drug discovery and development
Published in Expert Review of Clinical Pharmacology, 2008
Ping Guan, Andrew Olaharski, Mark Fielden, Nigel Roome, Yvonne Dragan, Joseph Sina
The screening of drug candidates to assess their carcinogenic potential has long been a challenge for drug development. While genotoxic compounds can be readily detected with a battery of standard tests, including short-term in vitro and in vivo assays, predicting nongenotoxic carcinogenicity remains a major challenge. The 2-year rodent bioassay has been held as the gold standard for the assessment of carcinogenic risk to humans. However, due primarily to the continuing doubt over their relevance to human risk assessment, there has been an increased demand for more efficient and accurate approaches to predict and understand human relevant risk of carcinogenicity. Novel biomarkers have helped to shed light on our understanding of the factors that lead to and are characteristic of the carcinogenic phenotypes. Tissue biomarkers of carcinogenicity identified to be concordant with drug exposures resulting in tumor outcome may assist the drug development process by resolving ambiguities, shortening timelines and enabling earlier decisions on compounds. This information could vastly improve the efficiency with which nongenotoxic carcinogens are identified and ensure earlier insight into the relevance for humans.
The World Health Organization defines hormone replacement therapy as carcinogenic: Is this plausible?
Published in Gynecological Endocrinology, 2008
Alfred O. Mueck, Harald Seeger
In June 2005 the World Health Organization's International Agency for Research on Cancer (IARC) classified combined hormone contraception and menopausal therapy as carcinogenic in humans. The IARC's function is to identify potential carcinogens associated with nutrition, environment and pharmaceutical products. They do not produce risk–benefit analyses for any country or population. Their conclusions are highly controversial in that no proof is presented for a causal relationship of estrogens with reproductive cancer, be it plausibility according to mechanisms of action or experimental evidence in an animal model. Equating natural compounds like estradiol with defined carcinogens like asbestos, tobacco smoke as well as indispensable drugs such as aspirin and tamoxifen is of no substantial clinical relevance. Thus, there are no new reasons to change current management principles with combination hormone contraception and therapy.