The effect of an hypoxic cell sensitizer on tumour growth delay and cell survival. Implications for cell survival in situ and in vitro

Abstract

Summary.-The effect of a single treatment with 30 mg dimethylnitrosamine (DMN) and 6 ,ug actinomycin D (ACT), given at different time intervals (ACT application to DMN, 2 h before, simultaneously, 5, 9 or 48 h later), was tested in female Sprague-Dawley rats in relation to renal carcinogenesis; additionally, the animals were fed either a normal or a protein deficient diet.The ACT treatment did not significantly modify either the kidney tumour incidence or the survival time in the different groups fed a normal diet. Nevertheless, there are indications that additional ACT application may shorten the latency period for DMN induced renal neoplasms or, when administered 5 h later than DMN, a slightly decreased and delayed tumour induction can be assumed. In groups fed a protein deficient diet, a significantly higher percentage of kidney tumour bearing animals as well as a shortened latency period were found when compared with the DMN group on normal diet, but these differences were independent of the additional ACT treatment 9 h later than DMN and were due to the protein deprivation. Morphologically, the tumours were of epithelial and mesenchymal type with a clear preponderance of the former type. Biochemical and morphological aspects are discussed.

Radiosensitizing and cytocidal effects on hypoxic cells of RO-07-0582, and repair of x-ray injury, in an experimental mouse tumour

“…4a shows that, when 1 mg/g of the electron-affinic radiosensitizer is given before irradiation, a large dosereduction factor or " sensitizer enhancement ratio " is obtained, between 2 0 and 2-4 over the dose range 18 to 25 Gy on the X-rays-only curve in air. This value is similar to other large values reported for several types of experimental tumour in mice using a variety of assay systems (Sheldon, Foster and Fowler, 1974;Denekamp and Harris, 1975;Brown, 1975;Begg, 1977;Sheldon and Hill, 1977;McNally, 1975;Stone and Withers, 1975;Rauth, Kaufman and Thomson, 1975;Bleehen, 1976;Denekamp and Stewart, personal communication). It differs however from the value of 1 0 reported by Hewitt for a cell-dilution experiment on this tumour, Squamous Carcinoma D, where two i.v.…”

Tumour volume response, initial cell kill and cellular repopulation in B16 melanoma treated with cyclophosphamide and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea

“…The repopulation studies reported here were found to confirm that cellular repopulation is more rapid after treatment with CCNU than after CY. The results presented here emphasize the complexity of the relationship between tumour-cell kill and growth delay (see also McNally, 1973McNally, ,1975aMcNally, , 1975bTwentyman, 1977). It would appear that the estimation of cell kill from tumour-growth delay data might be very difficult, although this has been attempted by Lloyd (1975) and by Griswold (1975).…”