Carcinogenesis and the plasma membrane.
Med Hypotheses
; 52(5): 367-72, 1999 May.
Article
en En
| MEDLINE
| ID: mdl-10416941
ABSTRACT
Presented is a two-stage hypothesis of carcinogenesis based on (1) plasma membrane defects that produce abnormal electron and proton efflux; and (2) electrical uncoupling of cells through loss of intercellular communication. These changes can be induced by a wide variety of stimuli including chemical carcinogens, oncoviruses, inherited and/or acquired genetic defects, and epigenetic abnormalities. The resulting loss of electron/proton homeostasis leads to decreased transmembrane potential, electrical microenvironment alterations, decreased extracellular pH, and increased intracellular pH. This produces a positive feedback loop to enhance and sustain the proton/electron efflux and loss of intercellular communication. Low transmembrane potential is functionally related to rapid cell cycling, changes in membrane structure, and malignancy. Intracellular alkalinization affects a variety of pH-sensitive systems including glycolysis, DNA synthesis, DNA transcription and DNA repair, and promotes genetic instability, accounting for the accumulation of genetic defects seen in malignancy. The abnormal microenvironment results in the selective survival and proliferation of malignant cells at the expense of contiguous normal cell populations.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Carcinógenos
/
Membrana Celular
/
Transformación Celular Neoplásica
/
Neoplasias
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Med Hypotheses
Año:
1999
Tipo del documento:
Article
País de afiliación:
Estados Unidos