Life and death in the genesis of the tumour cell

Abstract

Most tumours arise because of an aberrant response of cells following exposure to chemicals deliberately ingested, for example cigarette smoke, or present as an environmental pollutant, for example dietary aflatoxin. Recent evidence has highlighted the importance of tumour suppressor genes and oncogenes in determining the response of a cell to potentially mutagenic or growth disrupting events. Many toxicants in vivo can cause apoptosis in a dose dependent manner. At low dose apoptosis is engaged, but with high exposure cells may undergo necrosis as cellular metabolism is catastrophically overwhelmed preventing the ordered set of events that constitute apoptosis from occurring. Mutations in genes that control deletion of potentially damaged cells result in overriding of death signals and may result in survival of a cell that otherwise should have been deleted. This gave rise to the concept of the `undead' cell — the aberrant cell that has escaped normal growth controls taking the first step towards cancer. However, not all cell lineages respond to injury in the same ways, and even the same gene may have quite varied effects depending on the cellular and tissue environment.