Survival Curves for Normal-tissue Clonogens: A Comparison of Assessments Usingin Vitro, Transplantation, orin SituTechniques

Abstract

A survey of survival curves in the literature, for clonogenic cells (clonogens) in normal tissues, highlights the following features: the sensitivity of some human and dog clonogens apparently is greater than that of their counterparts in mice and sheep, assessed in vitro. However, this should be interpreted with caution because of the possibility of cell selection and the ability to modify sensitivity markedly in some systems by variations in growth conditions; extrapolation numbers are in general higher when assessed in vivo than in vitro. This is due partly to the lack of measurements of repair of potentially-lethal damage using many assays in vitro. This feature increases the extrapolation number when measured using transplantation assays in vivo; epithelial clonogens in vivo demonstrate a remarkable similarity in sensitivity between tissues. The range is similar for clonogens assayed in situ or by transplantation, and this argues against the possibility that a resistant subpopulation may be selected in most assays in situ. It is emphasized from the comparisons that caution must be exercised in extrapolating results, obtained for clonogens assayed in vitro or by transplantation in vivo, to the situation in situ.

Increasing the susceptibility of the rat 208F fibroblast cell line to radiation-induced apoptosis does not alter its clonogenic survival dose-response

“…For example, haemopoietic cell types are often radiation sensitive, while hepatocytes are relatively radiation resistant (Hendry, 1985). Similarly, lymphomas are typically responsive to irradiation, while melanomas often respond poorly (Steel, 1989).…”

ICRP Publication 131: Stem Cell Biology with Respect to Carcinogenesis Aspects of Radiological Protection

“…These clonogenic assays also showed that bone-marrow-derived progenitor cells were more radiosensitive than epithelial clonogenic cells ( Fig. 2.4) (Hendry, 1985). The exact molecular mechanism of PLDR has not been elucidated, but ataxia telangiectasia mutated (ATM), the master gene of radiation damage response, has been suggested to be involved in the process; however, a number of uncertainties are yet to be resolved (Lobrich and Jeggo, 2005).…”

“…Hence, it is reasonable that tissue stem cells exhibit a large capacity of PLDR as shown by in-vivo and in-situ clonogenic assays (Fig. 2.4) (Hendry, 1985). (40) Quiescence of stem cells poses two problems to the strategy of tissue stem cells in maintaining the integrity of the genome.…”

“…The separation between the dashed and solid lines for each tissue type indicates potentially lethal damage repair; note the positive effect in the case of mammary and thyroid epithelial cells, and liver (hepatocytes), and the negative effect for marrow spleen colony-forming units assayed in vivo (CFU-S) considered due to a radiation-induced differentiation effect. Source: Hendry (1985). Reproduced with permission from Informa. …”

Radiation-induced DNA damage in canine hemopoietic cells and stromal cells as measured by the comet assay

“…In contrast, the environment supporting the hemopoietic tissue, i.e., the hemopoietic stromal cells in the bone marrow (BM), are clearly more resistant [see reviews by Hendry and Lord, 1983;Hendry, 1985;Laver, 1989;Nothdurft, 19911. Canine hemopoietic cells are particulary radiosensitive.…”