Behaviour of Intracerebral Autografts of Mouse Tail Skin pre-treated with a Single Application of 20-Methylcholanthrene

Spencer, A. T.; Smith, William Thomas Lingwood

doi:10.1038/207649a0

Cited by 7 publications

(1 citation statement)

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“…These findings indicate that the mutagenic potential of the pellet is insufficient for the initiation of an experimental brain tumor. A synergy may also exist between the carcinogenic and physically irritative properties of the compound, as tumor incidence is greater when the carcinogen is administered as a solid rather than as a liquid or powder (Spencer and Smith 1965;Zimmerman 1969). These findings are consistent with the notion that disturbed tissue topography underlies tumor development (Rubin 1985;Sonnenschein and Soto 1999).…”

Section: Activated Macrophages and Glia Disrupt The Brain Microenvirosupporting

confidence: 81%

Perspectives on Brain Tumor Formation Involving Macrophages, Glia, and Neural Stem

Seyfried¹

2001

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The incidence of brain tumors is rising in children and the elderly, but little is known about the mechanisms underlying brain tumor initiation and progression. In the 1940s, Zimmerman and coworkers exploited the tumor-promoting potential of polycyclic hydrocarbons to produce brain tumor models in adult mice that simulated the neuropathology of human brain tumors. Based on these early findings and on recent neurobiological studies of stem cells, I propose that crystalline carcinogenic pellets surgically implanted in the central nervous system establish over time a microenvironment that fosters proliferation and genetic damage in neural stem cells and their progenitors. Moreover, activated glia (microglia and astrocytes) and recruited macrophages mediate these processes. Gradually local tissue fields, which normally restrict stem cell proliferation, become disorganized, leading to further stem cell proliferation, genetic damage, and eventual neoplasia. Depending on age, location, and the state of glial/macrophage activation, the resulting brain tumor may resemble transformed neural progenitors aborted in more or less differentiated states. This hypothesis integrates the general mechanisms by which neural stem cells, glia, and macrophages orchestrate the initiation and progression of brain cancer. Also discussed are implications of these concepts for the diagnosis and therapy of human brain tumors.

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Section: Activated Macrophages and Glia Disrupt The Brain Microenvirosupporting

confidence: 81%