Dose-Response Thresholds for Progressive Diseases

Do dose response thresholds exist for genotoxic alkylating agents?

The demonstration and acceptance of dose response thresholds for genotoxins may have substantial implications for the setting of safe exposure levels. Here we test the hypothesis that direct-acting DNA reactive agents may exhibit thresholded dose responses. We examine the potential mechanisms involved in such thresholded responses, particularly in relation to those of alkylating agents. As alky...

4. Dose response and potential thresholds in gene expression

The Key Events Dose-Response Framework: A Cross-Disciplinary Mode-of-Action Based Approach to Examining Dose-Response and Thresholds

The ILSI Research Foundation convened a cross-disciplinary working group to examine current approaches for assessing dose-response and identifying safe levels of intake or exposure for four categories of bioactive agents-food allergens, nutrients, pathogenic microorganisms, and environmental chemicals. This effort generated a common analytical framework-the Key Events Dose-Response Framework (K...

Stochastic thresholds: a novel explanation of nonlinear dose-response relationships for stochastic radiobiological effects.

New research data for low-dose, low-linear energy transfer (LET) radiation-induced, stochastic effects (mutations and neoplastic transformations) are modeled using the recently published NEOTRANS(3) model. The model incorporates a protective, stochastic threshold (StoThresh) at low doses for activating cooperative protective processes considered to include presumptive p53-dependent, high-fideli...

Carcinogenic risk assessment: are there dose thresholds for carcinogens?

While it has been generally accepted that genotoxic carcinogens have no dose threshold for their carcinogenic potential, there is increasing evidence that very low doses in fact are incapable of inducing tumours or preneoplastic lesions. Thus not only so-called epigenetic 'non-genotoxic' compounds like phenobarbital and benzene hexachloride, but also unequivocally genotoxic carcinogens like the...