Survival curve slope

Orth, D. S., Anderson Lutes, C. M., Smith, D. K., Milstein, S. R., 1989. Synergism of preservative system components Use of the survival curve slope method to demonstrate anti Pseudomonas synergy of methylparaben and acryUc add homopolymer/copolymers in vitro. J. Soc. Cosmet. Chem. 40, pp. 347 365. 

The relative toxicities of the cis and trans isomers of the platinum(II) neutral complexes, can be defined by the slopes of the survival curves (Dq) obtained by treating Hela cells in culture. Comparison of these two sets of values indicated that the relative abilities of cis and trans-DPP compounds to crosslink DNA in vivo (but not in vitro) were related to their cytotoxic action ( 9,3 ). These studies therefore suggest that interstrand crosslinking with both the platinum(II) compounds, but not necessarily platinum(IV) compounds, may be important in inducing their cytotoxic effects and that the cis isomer is most effective in inducing the reaction. 

The determinants of sterility assurance that must be considered in determining appropriate treatment levels to achieve particular SALs (in this text it will be assumed that the target SAL is lO ) or in validating existing treatment levels are, therefore, bioburden (microorganisms contaminating the item prior to treatment) and the shape and slope of the survival curve. 

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). 

Tailed Survival Curves Tailed survival curves cannot be extrapolated. They are characterized by a slope that diminishes with increasing exposure to the sterilization treatment. They are often described as concave. ... 

A plot of In 5 against t is then a straight line, with negative slope equal to a. An example, from Burch (2), is shown in Fig. 1, and another example, from Cameron and Pauling (3), in Fig. 2. Sometimes, as has been pointed out in a recent discussion (4), resolution of the survival curve into the sum of two or more Hardin Jones exponentials, with death rates Oi and coefficients can be made ... 

Figure 2 shows the influence of 1 to 5 mAf BZA on X-ray-induced killing. It can be seen that BZA treatment for 24 h after irradiation, did not change the slope of the survival curve. There was only a small reduction in the extrapolation number. A similar observation was also made with NA treatment (data not shown). 

Fig. 3 shows the survival of cells exposed to MNNG at various concentrations for 1 hr, followed by exposure to nalidixic acid at 100 xg for 20 hr in fresh medium. It can be observed diat nalidixic acid increased the killing by MNNG at all doses. The slope of the survival curve was also increased. Treatment of normal undamaged cells with 100 pg/ml of nalidixic acid did not affect their colony forming ability. 

These points also explain the semantic differences between a modifier or potentiator of radiation damage (by whatever mechanism) and a sensitizer (implying oxygen-mimetic or electron-accepting mechanisms) although the literature is not always consistent on this point. The radiation potentiation of platinum amine complexes in vitro is remarkably, and somewhat frustratingly, dependent on experimental conditions such as the time of incubation before irradiation and the phase of the cell cycle used occasional protection has even been seen by most workers. Consideration of these factors requires careful analysis of the shape and slope of the survival curves and is beyond the scope of this summary, but the factors need to be known for a complete description of the potentiating effect. 

The great importance of fluence has led to the introduction of a fluence related parameter to describe radiation effects of charged particles. Since empirically it Is found that dose- or fluence effect curves are linear for heavier particles at low energies, a single parameter Is sufficient to represent the survival curve the inactivation cross section o. ft Is defined as the slope of the fluence effect curve ... 

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

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... 

As noted above, some survival curves have zero initial slope that can be well fitted by hit functions of the form QC, or quadratic-... 

In Figure 7, we have plotted yet another similar set of data for ade2 forward mutations in a wild-type haploid strain. Again, the survival curve is biphasic LQk), and mutation induction is linear over an unusually wide range of dose. (A high dose decline in frequency probably occurs above 1000 ergs/ mm. ) For such a LQk,Lm) kinetic pattern, we would expect to find a yield curve with nonzero initial slope and a maximum at /2LD14 within the limits of the data, these expectations appear to be met. 

Note that ki is the initial slope of the (log) survival curve. If this slope is zero, then either Vc or r c n ust be unity if it is nonzero, then neither Tc nor Tmc can be unity. And, on this model, if there is no constitutive level of either EFR or EPR, then cannot be zero. Furthermore, if the mutation-induction process contains a linear component m 0), then there must exist a constitutive level of EPR r nc 0), and the efficiency of EFR as a — 0 cannot approach unity (r 1). 

Eq. (44)). In Eig. 20, we show the result of this approximation for reasonable a = 1 and cOc = 2 a/ Q )D- Even though these curves resemble the experimental data better than in the previous figure, they do not really provide more material support for the theory than the earlier method. This discussion simply demonstrates that the basic estimates are robust enough to survive different levels of treatment. Also, curiously, these curves reflect the experimental tendency that the higher T plateaus seem to have a more negative slope as compared to the low T ones (see Fig. 1), which was less obvious in Fig. 19. 

Q10 (temperature coefficient) The increase in the rate of a chemical process due to raising the temperature by 10 C. quantal responses Are all-or-none responses, or qualitative responses, e.g. death or survival (in contrast to quantitative responses which are continuous variables). The underlying distribution is the binomial distribution. Log dose-response lines for quantal responses are frequently sigmoidal in shape, and since this is the same form as the integrated frequency distribution curve, the slope of the... 

Figure 6 Diffusional scaling. Shown as a function of time are P, the average survival probability, and Z, 5, L the average wavefunction extent, on a log/log scale, as computed for three values of the coupling strength in the strongly delocalized limit, log( Af> ) = 2.8, 3.3, and 3.8. The straight line with slope indicated on the figure shows the power law fit to P(t). For each curve showing computational results the time has been multiplied by D = 11<1)7h.

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.

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