In other words, if there is a single effector Nutlin-3a in vivo and there are no subpopulations with different sensitivities, the relative length of the two branches of the response only depends on dosage,
not on time, which impedes the progressive predominance of one branch over the other, as can be seen in the response to nisin (Figure 2). It is difficult to specify a priori the characteristics of an effector able to produce a hormetic response in a given organism. Thus, phenol was selected for comparison because three features suggest its adequacy for this purpose: 1) it can be considered a single effector, as the weakly acidic character of its hydroxylic hydrogen makes only a negligible proportion of the ionic form in the assay conditions; 2) it is a well known, vigorous and not very specific antiseptic; 3) phenols are obligatory steps in the biodegradation of the aromatic hydrocarbons, a process which is initiated in many organisms by an active enzyme induction with a detoxifying role. The response obtained with C. piscicola (Figure 5), a stable stimulatory branch at low doses that did not progress over time at the expense of the inhibitory branch, is solid MAPK inhibitor evidence in favour of a hormetic phenomenon. Conclusions The responses of L. mesenteroides to nisin and
C. piscicola to pediocin showed variation over time, which generated anomalous DR profiles far from the simple sigmoid model. Some of these profiles were of the biphasic type with two branches of opposite sign, a characteristic that is usually attributed to a hormetic phenomenon. Our results show, however, that the combination of the kinetic model of microbial growth and the probabilistic model of DR relationships can generate time series with very different profiles, including all the anomalies detected in practice. In a complementary way, the dynamic model developed satisfactorily fits the most remarkable trends of the experimental time
succession of responses, when we accept that the microbial populations assayed contain-or develop during the exposure time-subpopulations with different sensitivity Mannose-binding protein-associated serine protease to bacteriocins. Therefore, although the biphasic profiles can be derived from a genuinely hormetic response, they can also arise when two effectors act on a bimodal-sensitive population [14, 15], or, as in the cases studied here, when a single effector acts on a unimodal-sensitive population. Any of these suppositions can be accurately described by means of a subtractive degenerate model (see Appendix), but to distinguish among them requires identification of the underlying mechanism. Toxicodynamic evidence in favour of the hormetic hypothesis could be the stability in the time of the dose intervals which define the two branches of the curve, as in the response of C. piscicola to phenol.
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