Carcinogenesis: Basic Principles

Abstract

Many steps are required to convert a normal cell into a cancerous one. The cancer cell must be able to multiply under conditions that a normal cell would not and to invade surrounding tissue and spread throughout the body. Both genetic changes, such as activation of oncogenes or inactivation of tumor suppressor genes, and epigenetic changes, such as stimulation of cell proliferation, contribute to the development of cancers. Chemical agents can increase the probability of malignant transformation by inducing mutations that can ultimately lead to tumor formation, by promoting the development of tumors in cells with preexisting genetic damage, or by increasing the rate of acquisition of malignant traits by benign tumors. Chemical carcinogens are structurally diverse, but all initiating agents are either already electrophiles or can be converted to electrophilic reactants through metabolic activation. Genetic and environmental factors can alter an individual's ability to metabolize carcinogens, to repair DNA damage, and to respond to mitogenic stimuli, all of which can alter susceptibility to chemical carcinogenesis. The incidence and time required for appearance of tumors appear to be dose-related, but the existence of no-effect doses of carcinogens remains controversial.

Reduced vitamin D receptor expression in parathyroid adenomas: implications for pathogenesis

“…Most research into the pathogenesis of parathyroid adenomas ( Hendy & Arnold, 1996), as of other benign endocrine tumours ( Shimon & Melmed, 1997), rests on the somatic mutation — clonal evolution paradigm ( Couch, 1996) that has been widely applied to the study of malignant tumours. A single cell with a mutation that confers a growth advantage on its progeny founds a new clone.…”

“…As the result of successive acquisition of additional mutations, each conferring an additional growth advantage, there evolves a subclone with the malignant phenotype. The growth promoting mutations lead either to transformation of a proto‐oncogene into an oncogene, or to loss of a tumour suppressor gene ( Couch, 1996). Both kinds of mutation have been found in parathyroid adenomas ( Hendy & Arnold, 1996), although no more than one in any tumour, and none has been demonstrated to be the initiating change present in the founder cell.…”

Encapsulated Pine Bark Polyphenolic Extract during Gastrointestinal Digestion: Bioaccessibility, Bioactivity and Oxidative Stress Prevention

“…As it is widely described, cancer development has many steps, from initiation and promotion to progression [40]. On this study it was evaluated the influence of bioactive compounds on the latest stage the progression.…”

Neoplastic transformation of human breast epithelial cells by estrogens and chemical carcinogens

“…It is generally accepted that malignant transformation involves genetic and epigenetic changes that derail common regulatory mechanisms, resulting in uncontrolled cellular proliferation and/or aberrant programmed cell death or apoptosis [Russo et al, 1988[Russo et al, , 1993a[Russo et al, ,b, 1996Holliday, 1996]. These cellular abnormalities, hallmarks of a carcinogenic process, are frequently associated with molecular alterations involving activation of protooncogenes and inactivation of tumor-suppressor genes as a result of genetic predisposition and/or exposure to physical (e.g., radiation), chemical (e.g., carcinogens, dietary components), and biological (e.g., viruses) environmental factors [Briand et al, 1987;Russo et al, 1988Russo et al, , 1993aRusso et al, ,b, 1996Russo et al, , 1998Band et al, 1990;Bartek et al, 1990;Soule et al, 1990;Tait et al, 1990;Garcia et al, 1991;Calaf and Russo, 1993;Couch 1996;Holliday, 1996;Hu et al, 1997]. A central challenge to cancer biology is the understanding of the cellular and molecular processes that drive a normal human breast epithelial cell to neoplastic growth.…”