Laboratory to Community: Chemoprevention Is the Answer

Olden, Kenneth; Vulimiri, Suryanarayana V.

doi:10.1158/1940-6207.capr-14-0124

Cited by 7 publications

(5 citation statements)

References 28 publications

(33 reference statements)

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“…However, as adducts do not equal mutations, there are several additional necessary key events proposed that require functioning cellular responses such DNA replication and cell division, prior to causing a mutation. Thus, formation of adducts, even pro-mutagenic ones, will not necessarily guarantee a mutagenic outcome [66, 67]. …”

Section: Alkylating Agentsmentioning

confidence: 99%

Contributions of DNA repair and damage response pathways to the non-linear genotoxic responses of alkylating agents

Klapacz

Pottenger

Engelward

et al. 2016

Mutation Research/Reviews in Mutation Research

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From a risk assessment perspective, DNA-reactive agents are conventionally assumed to have genotoxic risks at all exposure levels, thus applying a linear extrapolation for low-dose responses. New approaches discussed here, including more diverse and sensitive methods for assessing DNA damage and DNA repair, strongly support the existence of measurable regions where genotoxic responses with increasing doses are insignificant relative to control. Model monofunctional alkylating agents have in vitro and in vivo datasets amenable to determination of points of departure (PoDs) for genotoxic effects. A session at the 2013 Society of Toxicology meeting provided an opportunity to survey the progress in understanding the biological basis of empirically-observed PoDs for DNA alkylating agents. Together with the literature published since, this review discusses cellular pathways activated by endogenous and exogenous alkylation DNA damage. Cells have evolved conserved processes that monitor and counteract a spontaneous steady-state level of DNA damage. The ubiquitous network of DNA repair pathways serves as the first line of defense for clearing of the DNA damage and preventing mutation. Other biological pathways discussed here that are activated by genotoxic stress include post-translational activation of cell cycle networks and transcriptional networks for apoptosis/cell death. The interactions of various DNA repair and DNA damage response pathways provide biological bases for the observed PoD behaviors seen with genotoxic compounds. Thus, after formation of DNA adducts, the activation of cellular pathways can lead to the avoidance a mutagenic outcome. The understanding of the cellular mechanisms acting within the low-dose region will serve to better characterize risks from exposures to DNA-reactive agents at environmentally-relevant concentrations.

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Section: Alkylating Agentsmentioning

confidence: 99%

Contributions of DNA repair and damage response pathways to the non-linear genotoxic responses of alkylating agents

Klapacz

Pottenger

Engelward

et al. 2016

Mutation Research/Reviews in Mutation Research

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show abstract

“…They argue that due to the complex mechanism of the Nrf2/Keap1/ARE signaling pathways that mediate CDDO-Im anti-tumorigenicity may activate other cellular processes, e.g., as inflammation, that eliminate or interfere with the progression and promotion of initiated cells resulting in an "apparent" threshold, which may not be valid for chronic exposure to very low doses of AFB1 in the absence of CDDO-Im. On the contrary, Olden and Vulimiri [201] supported the arguments given by…”

Section: Natural and Socioeconomic Challengesmentioning

confidence: 82%

“…The study has attracted wide interest from peer scientists with both admiration and criticism not only for its rational experimental design and for providing an additional proof-of-principal for the high potency of CDDO-Im and potential to ensure complete protection against CCH, but also for reviving the debate on the "no-threshold/linear" vs "threshold/non-linear" dose-response paradigms in quantitative risk assessment of genotoxic hazards. Nonetheless, the claim about the non-linear dose-response relationship at very low doses and the applicability of the results to humans have raised some reservations [200][201] recognizing the valuable contribution of the study to the advance of knowledge in the field, Eaton…”

Section: Natural and Socioeconomic Challengesmentioning

confidence: 99%

Retrospective and Prospective Look at Aflatoxin Research and Development from a Practical Standpoint

Benkerroum

2019

Preprint

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Among the array of structurally and toxicologically diverse mycotoxins, aflatoxins have attracted the most interest of scientific research due to their high toxicity and incidence in foods and feeds. Despite the undeniable progress made in various aspects related to aflatoxins, the ultimate goal consisting of reducing the associated public health risks worldwide is far from being reached due to multiplicity of social, political, economic, geographic, climatic, and development factors. However, a reasonable degree of health protection is attained in industrialized countries owing to their scientific, administrative, and financial capacities allowing them to use high-tech agricultural management systems. Less fortunate situation exists in equatorial and sub-equatorial developing countries mainly practicing traditional agriculture managed by smallholders for subsistence, and where the climate is suitable for mould growth and aflatoxin production. A situation that worsens by the climatic change being increasingly suitable for aflatoxigenic mold growth and toxin production. Accordingly, it is difficult to harmonize the regulatory standards of aflatoxins worldwide, which prevents agri-foods of developing countries from access to the market of industrialized countries. To tackle the multi-facetted aflatoxin problems, actions should be taken collectively by the international community involving scientific research, technological and social development, environment protection, awareness promotion, etc. International cooperation should foster technology transfer and exchange of pertinent technical information. This review presents the main historical discoveries leading to our present knowledge on aflatoxins and the challenges that should be addressed presently and in the future at various levels to ensure higher health protection for everybody. In short, it aims to elucidate where we come from and where we should go in terms of aflatoxin research/development.

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“…They argue that the complex mechanism of the Nrf2/Keap1/ARE signaling pathways that mediate CDDO-Im anti-tumorigenicity may also activate other cellular processes, e.g., anti-inflammation, and eliminate or interfere with the progression and promotion of initiated cells resulting in an “apparent” threshold, which may not be valid for chronic exposure to very low doses of AFB1 in the absence of CDDO-Im. On the contrary, Olden and Vulimiri [201] supported the arguments given by Johnson, Egner, Baxter [196] for the non-linearity of the dose-response relationship. Moreover, Eaton and Schaupp [200] questioned the putative chemoprotective efficacy of CDDO-Im in humans as was demonstrated in rats.…”

Section: Challenges and Prospects For Aflatoxin Researchmentioning

confidence: 85%

“…The study has attracted wide interest from peer scientists with both admiration and criticism not only for its rational experimental design and for providing an additional proof-of-principal for the high potency of CDDO-Im and potential to ensure complete protection against CCH, but also for reviving the debate on the “no-threshold/linear” vs. “threshold/non-linear” dose-response paradigms in quantitative risk assessment of genotoxic hazards. Nonetheless, the claim about the non-linear dose-response relationship at very low doses and the applicability of the results to humans have raised some reservations [200,201]. While recognizing the valuable contribution of the study to the advance of knowledge in the field, Eaton and Schaupp [200] scrutinize the study and expressed skepticism about some interpretations.…”

Section: Challenges and Prospects For Aflatoxin Researchmentioning

confidence: 99%

Retrospective and Prospective Look at Aflatoxin Research and Development from a Practical Standpoint

Benkerroum

2019

IJERPH

View full text Add to dashboard Cite

Among the array of structurally and toxicologically diverse mycotoxins, aflatoxins have attracted the most interest of scientific research due to their high toxicity and incidence in foods and feeds. Despite the undeniable progress made in various aspects related to aflatoxins, the ultimate goal consisting of reducing the associated public health risks worldwide is far from being reached due to multiplicity of social, political, economic, geographic, climatic, and development factors. However, a reasonable degree of health protection is attained in industrialized countries owing to their scientific, administrative, and financial capacities allowing them to use high-tech agricultural management systems. Less fortunate situations exist in equatorial and sub-equatorial developing countries mainly practicing traditional agriculture managed by smallholders for subsistence, and where the climate is suitable for mould growth and aflatoxin production. This situation worsens due to climatic change producing conditions increasingly suitable for aflatoxigenic mould growth and toxin production. Accordingly, it is difficult to harmonize the regulatory standards of aflatoxins worldwide, which prevents agri-foods of developing countries from accessing the markets of industrialized countries. To tackle the multi-faceted aflatoxin problem, actions should be taken collectively by the international community involving scientific research, technological and social development, environment protection, awareness promotion, etc. International cooperation should foster technology transfer and exchange of pertinent technical information. This review presents the main historical discoveries leading to our present knowledge on aflatoxins and the challenges that should be addressed presently and in the future at various levels to ensure higher health protection for everybody. In short, it aims to elucidate where we come from and where we should go in terms of aflatoxin research/development.

show abstract

Laboratory to Community: Chemoprevention Is the Answer

Cited by 7 publications

References 28 publications

Contributions of DNA repair and damage response pathways to the non-linear genotoxic responses of alkylating agents

Contributions of DNA repair and damage response pathways to the non-linear genotoxic responses of alkylating agents

Retrospective and Prospective Look at Aflatoxin Research and Development from a Practical Standpoint

Retrospective and Prospective Look at Aflatoxin Research and Development from a Practical Standpoint

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