TOXICOLOGICAL SCIENCES, 143(1), 2015, 1–2 doi: 10.1093/toxsci/kfu241 LOOK INSIDE TOXSCI
Look Inside ToxSci
Editor’s Highlights
Tungsten and the tumor microenvironment
Aryl hydrocarbon receptor and lactation
Treatment of cancer requires aggressive approaches, which often have adverse side effects. A cohort of women who were subjected to intraoperative radiotherapy had tungsten-based shields implanted to minimize off target toxicity. Tungsten could be detected in the patients’ urine years after the surgery. There are numerous ways for a chemical to contribute to carcinogenesis, whether it be initiation by direct mutation of a DNA base or promotion by turning on a tumor promoter gene. Bolt and associates (pp. 165–177) examined the effects of tungsten in an animal model and showed that while tungsten did not promote tumor growth it did alter the tumor microenvironment in a manner that supported metastasis. These findings demonstrate that tungsten is not as inert as once thought and its use in cancer interventions may need to be revisited. View abstract.
Infants rely on adults for all of their needs. No more is this more evident than the process of lactation. Lactation is regulated by the hypothalamic-pituitary axis. Epidemiological studies have suggested that dioxin and related chemicals can disrupt lactation, but how this occurs has not been understood. In this issue of the journal, Basham et al. (pp. 36–45) demonstrate that dioxin and other aryl hydrocarbon receptor (AhR) agonists can directly block milk production in isolated mammary epithelial cells. More importantly, this effect appears to be mediated by the AhR repressor, which can block the transcription of the milk-related gene beta-casein. Identification of the connection between AhR signaling and lactation represents an important advance for understanding how environmental chemicals can disrupt this important biological process. View abstract.
Particle acceleration and chromium Drinking water standards for chromium are based on the combined total of trivalent and hexavalent chromium. Thompson and colleagues (pp. 16–25) employed x-ray fluorescence spectromicroscopy (microXRF) to image chromium content along the surface of the duodenum, where it is typically absorbed. MicroXRF requires a synchrotron light source. Synchrotrons are a type of particle accelerator, in which the guiding magnetic field and the particle beam are synchronized (different from the cyclotron that does not synchronize the magnetic field and beam). The authors used this approach to monitor the distribution of chromium along the microvilli and crypts of the intestinal lining to draw associations between chromium and tumor incidence and found that a very small proportion of the hexavalent chromium reaches the vulnerable areas. The use of this sophisticated approach revealed that current interpretation of hexavalent chromium exposure and cancer risk may need to be reconsidered. View abstract.
Multi-compartment pharmacokinetic model of lithium Lithium, atomic weight of 7, was in the original formulation of the soft drink 7-Up (not unlike the trace amounts of cocaine found in Coca-Cola in the early 1900s) and has even been written about in popular verse (I’m so happy cause today. . .). Lithium salts have long been known to stabilize mood and it is an important component of the treatment of bipolar disorder. With its narrow therapeutic window, changes in hydration state or inadvertent or intentional dose escalation can result in serious adverse effects, including severe neurotoxicity. Therefore, understanding the pharmacokinetics of lithium is essential for the proper treatment of bipolar disorder and associated conditions. Hanak and colleagues (pp. 185–195) developed a multicompartment model that included erythrocyte, plasma, cerebrospinal fluid, and brain lithium levels under 3 distinct models of poisoning: acute exposure, chronic overexposure, and acute on chronic exposure. Their results reveal complicated pharmacokinetic patterns depending on the various administration patterns. These results could prove useful in monitoring patients experiencing lithium toxicity. View abstract.
C The Author 2014. Published by Oxford University Press. V
All rights reserved. For Permissions, please e-mail: [email protected]
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Downloaded from http://toxsci.oxfordjournals.org/ at University of Pennsylvania Library on June 27, 2015
Data sharing represents a major challenge for the field of toxicology. We are generating data with ever-increasing speeds, and the infrastructure for storing and sharing is lagging behind. I encourage you to read my editorial on the topic and to help the field overcome the barriers that restrict optimal use of our data. Peer review is at the heart of the publication process. All manuscripts and letters published in ToxSci undergo extensive peer review. Even my commentary and highlights are subjected to review, but the system is not perfect. Readers are encouraged to read the Letter to the Editor on the next page that corrects a statement that I penned in a September Editorial Highlight. I have stated before that ToxSci welcomes feedback from our readers; it is what makes the journal so strong. Papers in the January issue provide insight into key mechanisms of action for several important toxicants, including dioxin, tungsten, lithium, cadmium, and arsenic, and utilize several cutting edge technologies, from synchrotron imaging to computational modeling. I encourage the readers to look inside ToxSci for the best original research in the field of toxicology.
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TOXICOLOGICAL SCIENCES, 2015, Vol. 143, No. 1
Letter to the Editor The Statement That Some Ochratoxins Are “. . .classified as human carcinogens” Is Not Accurate To the Editor,
REFERENCES Bui-Klimke, T. R., and Wu, F. (2014). Ochratoxin A and human health risk: a review of the evidence. Crit. Rev. Food Sci. Nutr. PMID: 24874522. Riley, R. T. (2014). Naturally occurring chemical carcinogens. In World Cancer Report 2014 (B. Stewart and C. P. Wild, Eds.), pp. 206–219. International Agency for Research on Cancer, Lyon, France. Ronald T. Riley* and J. David Miller† *Toxicology and Mycotoxin Research Unit, USDA-ARS, 950 College Station Road, Athens, Georgia 30605, Fax: (706) 546-3116, E-mail: [email protected]; and †Department of Chemistry, Carleton University, Ottawa, Ontario, Canada K1S5B6, Fax: þ1 613 520-3749, E-mail: [email protected] doi: 10.1093/toxsci/kfu214 Published by Oxford University Press 2014. This work is written by US Government employees and is in the public domain in the US.
Downloaded from http://toxsci.oxfordjournals.org/ at University of Pennsylvania Library on June 27, 2015
We are writing in response to a statement made in the recent “Editor’s Highlights” of the paper on ochratoxin and the microbiome (Toxicological Sciences, 141(1), 2014, 1). Ochratoxins, like the other agriculturally important mycotoxins, are natural contaminants and must be managed on a risk basis. Unfortunately, the assertion that some ochratoxins “. . .have been classified as human carcinogens” is not correct. A better way to characterize this toxin would be “that ochratoxin A has been shown to be carcinogenic in animal models.” This is the evaluation of the International Agency for Research on Cancer (IARC) making ochratoxin A Group 2B (possible human carcinogen). The United States National Toxicology Program (USNTP) classifies them as reasonably anticipated to be a human carcinogen. The only mycotoxins that are known human carcinogens are aflatoxins; IARC Group 1 and USNTP “known to be a human carcinogen” (Riley, 2014). Although this may seem to be a minor point, regulating ochratoxin concentrations in cereal grains as if they were as dangerous as aflatoxins seems unwise. Additional costs would accrue to U.S. and Canadian agriculture for little or no discernible public health benefit (Bui-Klimke and Wu, 2014).
For this reason alone, caution should be exercised when making statements about the carcinogenic/mutagenic risk of mycotoxins to humans.
Look Inside ToxSci
Editor’s Highlights
Tungsten and the tumor microenvironment
Aryl hydrocarbon receptor and lactation
Treatment of cancer requires aggressive approaches, which often have adverse side effects. A cohort of women who were subjected to intraoperative radiotherapy had tungsten-based shields implanted to minimize off target toxicity. Tungsten could be detected in the patients’ urine years after the surgery. There are numerous ways for a chemical to contribute to carcinogenesis, whether it be initiation by direct mutation of a DNA base or promotion by turning on a tumor promoter gene. Bolt and associates (pp. 165–177) examined the effects of tungsten in an animal model and showed that while tungsten did not promote tumor growth it did alter the tumor microenvironment in a manner that supported metastasis. These findings demonstrate that tungsten is not as inert as once thought and its use in cancer interventions may need to be revisited. View abstract.
Infants rely on adults for all of their needs. No more is this more evident than the process of lactation. Lactation is regulated by the hypothalamic-pituitary axis. Epidemiological studies have suggested that dioxin and related chemicals can disrupt lactation, but how this occurs has not been understood. In this issue of the journal, Basham et al. (pp. 36–45) demonstrate that dioxin and other aryl hydrocarbon receptor (AhR) agonists can directly block milk production in isolated mammary epithelial cells. More importantly, this effect appears to be mediated by the AhR repressor, which can block the transcription of the milk-related gene beta-casein. Identification of the connection between AhR signaling and lactation represents an important advance for understanding how environmental chemicals can disrupt this important biological process. View abstract.
Particle acceleration and chromium Drinking water standards for chromium are based on the combined total of trivalent and hexavalent chromium. Thompson and colleagues (pp. 16–25) employed x-ray fluorescence spectromicroscopy (microXRF) to image chromium content along the surface of the duodenum, where it is typically absorbed. MicroXRF requires a synchrotron light source. Synchrotrons are a type of particle accelerator, in which the guiding magnetic field and the particle beam are synchronized (different from the cyclotron that does not synchronize the magnetic field and beam). The authors used this approach to monitor the distribution of chromium along the microvilli and crypts of the intestinal lining to draw associations between chromium and tumor incidence and found that a very small proportion of the hexavalent chromium reaches the vulnerable areas. The use of this sophisticated approach revealed that current interpretation of hexavalent chromium exposure and cancer risk may need to be reconsidered. View abstract.
Multi-compartment pharmacokinetic model of lithium Lithium, atomic weight of 7, was in the original formulation of the soft drink 7-Up (not unlike the trace amounts of cocaine found in Coca-Cola in the early 1900s) and has even been written about in popular verse (I’m so happy cause today. . .). Lithium salts have long been known to stabilize mood and it is an important component of the treatment of bipolar disorder. With its narrow therapeutic window, changes in hydration state or inadvertent or intentional dose escalation can result in serious adverse effects, including severe neurotoxicity. Therefore, understanding the pharmacokinetics of lithium is essential for the proper treatment of bipolar disorder and associated conditions. Hanak and colleagues (pp. 185–195) developed a multicompartment model that included erythrocyte, plasma, cerebrospinal fluid, and brain lithium levels under 3 distinct models of poisoning: acute exposure, chronic overexposure, and acute on chronic exposure. Their results reveal complicated pharmacokinetic patterns depending on the various administration patterns. These results could prove useful in monitoring patients experiencing lithium toxicity. View abstract.
C The Author 2014. Published by Oxford University Press. V
All rights reserved. For Permissions, please e-mail: [email protected]
1
Downloaded from http://toxsci.oxfordjournals.org/ at University of Pennsylvania Library on June 27, 2015
Data sharing represents a major challenge for the field of toxicology. We are generating data with ever-increasing speeds, and the infrastructure for storing and sharing is lagging behind. I encourage you to read my editorial on the topic and to help the field overcome the barriers that restrict optimal use of our data. Peer review is at the heart of the publication process. All manuscripts and letters published in ToxSci undergo extensive peer review. Even my commentary and highlights are subjected to review, but the system is not perfect. Readers are encouraged to read the Letter to the Editor on the next page that corrects a statement that I penned in a September Editorial Highlight. I have stated before that ToxSci welcomes feedback from our readers; it is what makes the journal so strong. Papers in the January issue provide insight into key mechanisms of action for several important toxicants, including dioxin, tungsten, lithium, cadmium, and arsenic, and utilize several cutting edge technologies, from synchrotron imaging to computational modeling. I encourage the readers to look inside ToxSci for the best original research in the field of toxicology.
2
|
TOXICOLOGICAL SCIENCES, 2015, Vol. 143, No. 1
Letter to the Editor The Statement That Some Ochratoxins Are “. . .classified as human carcinogens” Is Not Accurate To the Editor,
REFERENCES Bui-Klimke, T. R., and Wu, F. (2014). Ochratoxin A and human health risk: a review of the evidence. Crit. Rev. Food Sci. Nutr. PMID: 24874522. Riley, R. T. (2014). Naturally occurring chemical carcinogens. In World Cancer Report 2014 (B. Stewart and C. P. Wild, Eds.), pp. 206–219. International Agency for Research on Cancer, Lyon, France. Ronald T. Riley* and J. David Miller† *Toxicology and Mycotoxin Research Unit, USDA-ARS, 950 College Station Road, Athens, Georgia 30605, Fax: (706) 546-3116, E-mail: [email protected]; and †Department of Chemistry, Carleton University, Ottawa, Ontario, Canada K1S5B6, Fax: þ1 613 520-3749, E-mail: [email protected] doi: 10.1093/toxsci/kfu214 Published by Oxford University Press 2014. This work is written by US Government employees and is in the public domain in the US.
Downloaded from http://toxsci.oxfordjournals.org/ at University of Pennsylvania Library on June 27, 2015
We are writing in response to a statement made in the recent “Editor’s Highlights” of the paper on ochratoxin and the microbiome (Toxicological Sciences, 141(1), 2014, 1). Ochratoxins, like the other agriculturally important mycotoxins, are natural contaminants and must be managed on a risk basis. Unfortunately, the assertion that some ochratoxins “. . .have been classified as human carcinogens” is not correct. A better way to characterize this toxin would be “that ochratoxin A has been shown to be carcinogenic in animal models.” This is the evaluation of the International Agency for Research on Cancer (IARC) making ochratoxin A Group 2B (possible human carcinogen). The United States National Toxicology Program (USNTP) classifies them as reasonably anticipated to be a human carcinogen. The only mycotoxins that are known human carcinogens are aflatoxins; IARC Group 1 and USNTP “known to be a human carcinogen” (Riley, 2014). Although this may seem to be a minor point, regulating ochratoxin concentrations in cereal grains as if they were as dangerous as aflatoxins seems unwise. Additional costs would accrue to U.S. and Canadian agriculture for little or no discernible public health benefit (Bui-Klimke and Wu, 2014).
For this reason alone, caution should be exercised when making statements about the carcinogenic/mutagenic risk of mycotoxins to humans.
