Radiobiological Studies of Cells in Multicellular Spheroids Using a Sequential Trypsinization Technique

Giesbrecht, J.; Wilson, WR; Hill, Richard P.

doi:10.2307/3575512

Cited by 21 publications

(11 citation statements)

References 14 publications

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“…2). This is consistent with the fact that, in terms of the radiobiological 02 effect, these cells are at an intermediate [02] when naturally hypoxic (Franko & Sutherland, 1979b;Giesbrecht et al, 1981 (Fig. 4).…”

Section: Discussionsupporting

confidence: 83%

“…Binding to the central 50 ,m of the viable rim is possibly enhanced, while no decrease in binding is seen for the inner half of the viable rim. Since 50% of the innermost cells lose their clonogenicity in 3 h under these conditions and 90% die in 6 h (Franko & Sutherland, 1978;Giesbrecht et al, 1981), it is apparent that the ability of cells to bind MISO is not directly related to viability. It might be that sterile hypoxic cells must become pyknotic or necrotic before they bind MISO at a reduced rate.…”

Section: Discussionmentioning

confidence: 99%

“…The volume of the region of full hypoxia depends on the extent of the reduction in [02], and can be predicted theoretically (Franko & Sutherland, 1979a;Giesbrecht et al, 1981). All cells in the spheroid can be fully oxygenated by increasing the [02] in the growtlh mnedium (Giesbrecht et al, 1981). A preliminary experiment (Chapman et al, 1981) showed enhanced binding of 14C-MISO to the first few cell layers sur-rounding the necrotic centres of V79 spheroids.…”

mentioning

confidence: 99%

“…The outer layers of cells are well oxygenated, an inner region of necrosis is present and cells near the necrotic centre are radiobiologically hypoxic (Sutherland & Durand, 1976;Franko & Sutherland, 1979a, b;Giesbrecht et al, 1981). FuLll radiobiological hypoxia can be induced by reducing the [02] in the growth medium (Franko & Sutherland, 1979b).…”

mentioning

confidence: 99%

“…FuLll radiobiological hypoxia can be induced by reducing the [02] in the growth medium (Franko & Sutherland, 1979b). The volume of the region of full hypoxia depends on the extent of the reduction in [02], and can be predicted theoretically (Franko & Sutherland, 1979a;Giesbrecht et al, 1981). All cells in the spheroid can be fully oxygenated by increasing the [02] in the growtlh mnedium (Giesbrecht et al, 1981).…”

mentioning

confidence: 99%

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Binding of 14C-misonidazole to hypoxic cells in V79 spheroids

Franko¹,

Chapman²

1982

Br J Cancer

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

mentioning

confidence: 99%

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Binding of 14C-misonidazole to hypoxic cells in V79 spheroids

Franko¹,

Chapman²

1982

Br J Cancer

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Importance of critical metabolites and cellular interactions in the biology of microregions of tumors

Sutherland

1986

Cancer

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Heterogeneity of cellular microenvironments and associated differences in phenotypic expression of cells in solid tumors occur as a consequence of deficiencies of vascularization. Intervascular microregions of tumors and micrometastases can be modeled by multicellular spheroids in vitro. These develop concentration gradients of critical metabolites such as oxygen, glucose, and probably also other important nutrients, hormones, and growth factors. Drug penetration may also be reduced. Concentrations of these factors decrease from the periphery towards the center, but gradients develop in the opposite direction for certain metabolic and necrotic products such as lactate and pH. Such gradients significantly modify the proliferative status of the cells, viability, clonogenicity, cell cycle distribution, antigen expression, and differentiation. Stress of oxygen and glucose deprivation induces synthesis of a specific set of proteins. Cellular interactions can also modulate phenotypic expression, including oxygen and glucose consumption rates and sensitivity to radiation and drugs. The mechanisms of these are unknown, but changes in cell-cell communication and DNA damage and repair have been demonstrated in spheroids. Microenvironmental and cellular changes may be transient. Thus, the characteristics of cells in tumor microregions may be quite different from the intrinsic cellular properties observed after growth of cells in standard culture systems. These changes may have significant effects on responses to therapeutic agents.

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Drug Penetration and Therapeutic Resistance

Minchinton

Kyle

2010

Tumor Microenvironment

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Radiobiological Studies of Cells in Multicellular Spheroids Using a Sequential Trypsinization Technique

Cited by 21 publications

References 14 publications

Binding of 14C-misonidazole to hypoxic cells in V79 spheroids

Binding of 14C-misonidazole to hypoxic cells in V79 spheroids

Importance of critical metabolites and cellular interactions in the biology of microregions of tumors

Drug Penetration and Therapeutic Resistance

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