Shouldered survival curves

Shouldered" Survival Curves Survival curves that initially show no sen sitivity to a sterilizatioa treatment but then respond in a typical exponential manner as exposure continues are referred to as shouldered." They conform to the mathematical form... 

For the purposes of exMpolating SALs, shouldered survival curves can be treated as exponential curves after making an appropriate allowance for the... 

FIGURE 4. Calculated yield and survival curves for biphasic, linear-quadratic killing (shouldered survival curve of the form LQk) and linear (L), quadratic (0, and biphasic, linear-quadratic (LQ) mutation induction over mutagen dose in arbitrary units (these units were chosen such that the numerical LDs values in both Figures 3 and 4 would be the same). The values of the coefficients of mutation and lethality used were = 10 (units)" mj = 10" (units)" kx = 10 (units)" ... 

For purely quadratic killing (which gives a shouldered survival curve with zero initial slope) and linear mutation induction, we can put ki and equal to zero in equation (22) so that we obtain... 

Before proceeding with biphasic cases involving a shouldered survival curve of the form LQk, we note that for such curves, the dose corresponding to z lethal hits (x ) is given by the solution of the quadratic expression... 

Another member of the FGF family, FGF-4, protects against radiation-iaduced ceU killing and enhanced the G2 arrest when overexpressed ia a human adrenal cortical carcinoma ceU line (196). This effect is again manifested as the appearance of a shoulder on the survival curve, although neither the control nor the transfected cells undergo radiation-iaduced apoptosis. No differences ia the yield or repair of either SSBs or DSBs have been observed. 

In order to compare mutation frequency induced by 220-MeV C ions with that by low-LET radiation (electrons), Arabidopsis visible phenotype loci were chosen as follows transparent testa tt) whose seed coat is transparent because of lack of pigment glaborous gl), which have no hair on their leaves and stems and long hypocotyl hy) whose hypocotyl is longer than that of the wild type in the light condition. Mutation frequencies of tt, gl, and hy induced by carbon ions were 8- to 34-fold higher than those by electrons (Table 2). In this study, irradiation doses for the induction of mutation were determined from the RBE of carbon ions compared with that of electrons on the survival of plants, which was approximately 5. Both doses are at three-quarters of the shoulder dose of each survival curve [104]. 

Clonogenic survival of B16 melanoma cells measured after exposure to graded doses of 211 At-AMT for 45 minutes is represented in Figure 12, showing that this radiolabelled modified melanin precursor is exceptionally cytotoxic. The linear cell survival curve, without a shoulder in the low-dose region, is characterisitc for high-LET a radiation125. 

Beside bioburden, the other determinant of sterility assurance is the survival curve and its shape and its slope. It is not correct to assume that all survival curves are of the simple linear type when data is plotted on semilogarithmic graph paper. Three general types of survival curve have been reported, the exponential curve, the shouldered" curve, and the "tailed" curve (Fig. 4). 

Survival and Mutagenesis from MMS. 3AB (1 vaM) caused a large increase in the toxicity of MMS, which was expressed predominantly by elimination of the shoulder of the survival curve (Table 1). The extrapolation number was reduced from 18.0 to 1.0, but the Do was not changed significantly. The mutation frequencies to ouabain resistance... 

In principle there is an exponential relationship between the microorganism survival and the absorbed dose. However, the practically measured survival curves often deviate from the linear relationship on the log survival-absorbed dose plots. At the beginning of the treatment there is a shoulder initially the survival decreases less steeply than at higher doses. It indicates that more than one lesion is required to kill the microorganism the shoulder is due to repair processes within the cells. 

Extensive discussion of radiobiological principles is beyond the scope of this chapter, yet a few definitions will be mentioned. The response of tumors to radiotherapy is determined by several factors such as repopulation, reoxygenation, number of clonogenic cells, and their intrinsic radiosensitivity. Since the introduction of mammalian cell survival curves, the parameters D and N have been used as quantitative measures of inherent radiation sensitivity, as was the shoulder width Dq (Thames and Suit 1986). Today the ratio alpha/beta is the most common parameter for characterization of cell survival curves. It is also a measure of fractionation sensitivity. 

In the liquid phase, time-survival curves of bacterial spores treated with formaldehyde have been reported to show initial shoulders, irrespective of whether aqueous or alcoholic solutions are used [62, 74], although this phenomenon has not been observed by other workers [75]. Various alcohols have also been shown to reduce the sporicidal activity of glutaraldehyde [62, 63]. 

The shape of the survival curves differs considerably. Whereas for photon irradiation the typically shouldered shape is observed, low energy carbon irradiation leads to an approximately linear dose response curve. 

Since the physical characteristics are exactly the same for all three cases, the differences of predicted RBE values can be entirely attributed to the different reference low-LET survival curves which are used as input for the calculation (they are shown as insert in Fig. 29). Obviously the RBE is correlated with the shoulder shape of the photon dose response curve for pronounced shoulders, significantly enhanced RBE values are predicted, whereas with decreasing shoulder width, decreasing RBE values are expected, and in the extreme case RBE should be close to one for cell systems showing purely exponential survival curves for photon radiation [141]. 

Other strains of diploid yeast have survival curves with zero initial slopes best approximated by H ix) = 4- Any of these shouldered sur-... 

The ease of oxidation of phosphines means that they are difficult to test reliably for biological activity, but oxidation also provides cells with an inbuilt resistance mechanism. Shoulders are often seen on cell survival curves. The donation of an oxygen atom to a phosphine can be a controlled, non-destructive 2-electron process. In cells one-electron acceptors are also available e.g. Cu(II), Fe(III), peroxy radicals. The ensuing radical chemistry could be very destructive especially it occurs in membranes. Membrane bound enzymes handling electrons (e.g. cytochrome oxidase, 4 one-electron processes are involved in the reduction of dioxygen to water) may be particular targets. 

Figure 18.5. A illustrates the effect of dosefractionation on cell survival at high doses and dose rates. After each succeeding dose fraction, the curve exhibits the same shoulder and slope, indicating that within a given period part or all of the damage is repaired.

When plotting the fraction of surviving cells as a function of dose, a typically shoulder shaped dose response curve is observed for most cell types (Fig. 6). This type of dose response curve is usually described by a linear-quadratic approach ... 

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