Response of human tumor cells to radiation and cytotoxic drugs
Abstract
Important differences between human cancers and
experimental animal tumours limit the potential of the latter as
models for cancer therapy research. This thesis describes the
development of a clonogenic assay for human tumour cells,
allowing for the first time the radiosensitivity and chemosensitivity
of these to be measured in a way previously restricted to cells
from experimental animal tumours and established tumour cell
lines. The technique involves the use of agar in diffusion chambers
implanted into murine peritoneal cavities, the mice acting both as
"incubators" and as a source of nutrients for cell growth. Human
tumour xenografts have been used for most experiments, although
the use of the assay to clone cells from human tumours taken direct
from the patient without xenograft passage has also been investigated. With this assay, the radiosensitivities of cells from several
human tumours were measured, both in vitro and in vivo, and the
dose survival curves so obtained provided information on the
mechanisms underlying the clinical response of different human
tumours to radiotherapy. The system was also used to demonstrate
the enhancing effect of the radiosensitising drug Ro-07-0582 on the
radiosensitivity of hypoxic tumour cells in vivo.
Studies on the sensitivity of human tumour cells to cytotoxic
drugs showed important differences compared with cells from
experimental animal tumours, and some correlation was shown between cell survival in the assay and clinical response to
chemotherapy.
The advantages of this assay over those based on animal
tumours as a tool to complement clinical cancer therapy research
are discussed, and suggestions are proposed for its further use.