Genotoxic effect of meat consumption: A mini review Pelland-St-Pierre, Laura; Sernoskie, Samantha Christine; Verner, Marc-André ...
Mutation research,
March-April 2021, 2021 Mar-Apr, 2021-03-00, Volume:
863-864
Journal Article
Peer reviewed
•A review was conducted to assess the genotoxic potential of meat consumption in humans.•Studies support a positive association between meat intake and biomarkers of genotoxicity.•Genotoxicity may ...play an important role in the meat-cancer association.•Statistical power, measurement error and confounding should be considered in future study design.
In 2015, the International Agency for Research on Cancer classified the consumption of processed meat as carcinogenic to humans (Group 1) and red meat as probably carcinogenic to humans (Group 2A) based on sufficient data from animal models and epidemiological studies. However, research characterising the mechanisms underlying this carcinogenic process in humans are limited, particularly with respect to measures of direct DNA damage. The current review sought to evaluate and summarize the recent literature, published since 2000, regarding the associations of meat consumption and three biomarkers of genotoxicity in humans: DNA strand breaks (measured using the comet assay), DNA adducts, and micronucleus formation. After screening 230 potential articles, 35 were included, and then were classified as experimental or observational in design, the latter of which were further categorized according to their dietary assessment approach. Among the 30 observational studies, 4 of which used two different assays, 3 of 5 comet assay studies, 13 of 20 DNA adduct studies, and 7 of 9 micronucleus studies reported a positive association between meat consumption and DNA damage. Among the 5 experimental studies, 1 of 1 using the comet assay, 3 of 3 measuring DNA adducts and 0 of 1 measuring micronuclei reported significant positive associations with meat consumption. Nevertheless, common limitations among the selected publications included small sample size, and poor methodological reporting of both exposure and outcome measures. Moreover, the vast majority of studies only measured DNA damage in one biological sample using a single assay and we cannot exclude the possibility of publication bias. Ultimately, our review of the literature, published since 2000, revealed a preponderance of studies that support mechanisms of genotoxicity in playing an important role in the meat-cancer association.
IntroductionSex hormones have been implicated in the etiology of colorectal cancer. Endocrine disruptors (EDCs) are compounds that can interfere with sex hormone signalling and cause adverse health ...effects, including cancer. Exposure to EDCs is ubiquitous, but exposure in some workplaces occurs at much higher levels than in the general population.ObjectiveTo determine whether occupational exposure to EDCs is associated with colorectal cancer risk.Material and MethodsA case-cohort study was nested in the Alberta’s Tomorrow Project (ATP) and in the Ontario Health Study (OHS). Incident cases of colorectal cancer were identified (NATP=202, NOHS=605); a sub-cohort of 3,464 participants was selected at baseline (NATP=565, NOHS=2,899). Occupational exposure to 17 EDCs was estimated via linkage to CANJEM, a job-exposure matrix, for participants’ longest-held job. Specifically, CANJEM provides a frequency-weighted intensity metric of exposure and it was used to categorize participants into never exposed, exposed and substantially exposed to each individual EDC. Multivariable logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for colorectal cancer associated with occupational exposure to EDCs while controlling for confounders identified using a directed acyclic graph.ResultsIn ATP, exposure to arsenic (OR=2.86, 95%CI: 1.06–7.63), copper (OR=0.53, 95%CI: 0.29–0.92), lead (OR=0.58, 95%CI: 0.34–0.97) and substantial exposure to arsenic (OR=2.87, 95%CI: 1.01–1.80), phenol (OR=0.25, 95%CI: 0.08–0.61), and trichloroethylene (OR=0.45, 95%CI: 0.21–0.90) were associated with colorectal cancer. In OHS, exposure to polychlorinated biphenyls (OR=3.95, 95%CI: 1.82–8.55), styrene (OR=0.47, 95%CI: 0.26–0.79), and substantial exposure to aluminum (OR=1.32, 95%CI: 1.03–1.68), cadmium (OR=0.59, 95%CI: 0.38–0.87), lead (OR=1.29, 95%CI: 1.03–1.60), phthalates (OR=0.52, 95%CI: 0.25–0.96), and trichloroethylene (OR=1.43, 95%CI: 1.08–1.88) were associated with colorectal cancer.ConclusionOf the 17 EDCs, five were associated with an increased risk, and seven with a decreased colorectal cancer risk; however, none of the associations were consistent between the two cohorts.
Electronic waste recycling (e-recycling) exposes workers to substances such as flame retardants and metals. Some of them are known or suspected endocrine disruptors that could affect hormonal ...homeostasis and eventually result in adverse health outcomes. Our aim was to measure biological concentrations of organophosphate ester (OPE) metabolites, polybrominated diphenyl ethers (PBDEs), mercury, lead and cadmium in e-recycling workers, and to explore associations with thyroid and sexual hormones.
In a cross-sectional study, end-of-shift blood and urine spot samples were collected from 23 women and 77 men in six e-recycling facilities and one commercial recycling facility. Urinary concentrations of 15 OPE metabolites and mercury, and blood concentrations of 12 PBDE congeners, lead, cadmium, and thyroid (thyroxine T4, triiodothyronine T3, thyroid stimulating hormone TSH) and sexual (testosterone T, estradiol, Follicle Stimulating Hormone FSH, Luteinizing hormone LH) hormones were measured.
E-recycling workers had higher concentrations of BDE209, all OPE metabolites, and lead than commercial recycling workers. In e-recycling workers, plasma geometric mean concentration of BDE209 was 18 ng/g lipids (geometric standard deviation GSD: 2.8) vs.1.7 ng/g lipids (GSD: 2.8) in commercial recycling, and urinary geometric mean concentration of diphenyl phosphate (DPhP), a major metabolite of triphenyl phosphate, was 1.7 ng/ml (GSD: 2.5), vs. 0.95 ng/ml (GSD: 2.0). In men, a two-fold increase in BDE209 was associated with 3.1% (95% Confidence interval: 0.07, 6.1) higher levels of total T4, and a two-fold increase in tert-butyl diphenyl phosphate (tb-DPhP) was associated with 18% (−29, −4.7) lower total T, 18% (−27, −6.9) lower free T and 13% (−25, 0.70) lower free T/estradiol ratio. In women, a two-fold increase in BDE153 was associated with 10% (−17, −3.2) lower free T3.
To our knowledge, this is the first study to show associations between OPE metabolites and sex hormones in adults. Although some of our results are not conclusive and need replication, they suggest that prudent avoidance should be applied in risk management of flame retardants.
Northeastern British Columbia (Canada) is an area of intense natural gas exploitation by hydraulic fracturing. Hydraulic fracturing can release contaminants, including trace metals, many of which are ...known developmental toxicants. To date, there is limited data on human exposure to contaminants in this region.
We aimed to examine trace metals in urine and hair samples from 29 Indigenous and non-Indigenous pregnant women from two communities (Chetwynd and Dawson Creek) in Northeastern British Columbia.
We recruited 29 pregnant women who provided spot urine samples over five consecutive days and one hair sample. We measured 19 trace metals in pooled urine samples from each participant and in the first 2 cm of hair closest to the scalp. We compared urinary and hair concentrations to those measured in women from the general population using data from the Canadian Health Measure Survey (CHMS), or reference values found in the literature for trace metals not measured in the CHMS.
Median urinary (0.49 μg/L) and hair (0.16 μg/g) concentrations of manganese were higher in our participants than in the CHMS (<0.05 µg/L in urine) or reference population (0.067 μg/g in hair). In hair, median values for barium (4.48 μg/g), aluminum (4.37 μg/g) and strontium (4.47 μg/g) were respectively 16, 3, and 6 times higher compared with median values in a reference population. Concentrations of barium and strontium in hair were higher in self-identified Indigenous participants (5.9 and 5.46 μg/g, respectively) compared to non-Indigenous participants (3.88 and 2.60 μg/g) (p-values = 0.02 and 0.03).
Our results suggest higher gestational exposure to certain trace metals in our study population compared to reference populations.
The World Health Organization recommends indoor residual spraying (IRS) of insecticides (including dichlorodiphenyltrichloroethane DDT) to fight malaria vectors in endemic countries. There is limited ...information on children's exposure to DDT in sprayed areas, and tools to estimate early-life exposure have not been thoroughly evaluated in this context.
To document serum p,p′-DDT/E levels in 47 mothers and children participating in the Venda Health Examination of Mothers, Babies and their Environment (VHEMBE), a study conducted in an area where IRS insecticides are used annually, and to evaluate the precision and accuracy of a published pharmacokinetic model for the estimation of children's p,p′-DDT/E levels.
p,p′-DDT/E levels were measured in maternal serum at delivery, and in children's serum at 12 and 24 months of age. A pharmacokinetic model of gestational and lactational exposure was used to estimate children's p,p′-DDT/E levels during pregnancy and the first two years of life, and estimated levels were compared to measured levels.
The geometric means of children's serum p,p′-DDT/E levels at 12 and 24 months were higher than those of maternal serum levels. Regression models of measured children's p,p′-DDT/E levels vs. levels estimated with the pharmacokinetic model (which only accounted for children's exposure through placental transfer and breastfeeding) had coefficients of determination (R2) ranging from 0.75 to 0.82. Estimated p,p′-DDE levels were not significantly different from measured levels, whereas p,p′-DDT levels were overestimated by 36% at 12 months, and 51% at 24 months.
Results indicate that children living in a sprayed area have serum p,p′-DDT/E levels exceeding their mothers' during the first two years of life. The pharmacokinetic model may be useful to estimate children's levels in the VHEMBE population.
•Children's p,p′-DDT/E levels at 12 and 24 months were higher than maternal levels.•The pharmacokinetic model of children's lactational exposure showed good precision.•Results suggested breastfeeding is the main contributor to children's exposure.•Pharmacokinetic modeling can be used to estimate children's levels in sprayed areas.
Abstract
Lipophilic persistent environmental chemicals (LPECs) can accumulate in a woman’s body and transfer to her developing child across the placenta and via breast milk. To assess health risks ...associated with developmental exposures to LPECs, we developed a pharmacokinetic (PK) model that quantifies mother-to-offspring transfer of LPECs during pregnancy and lactation and facilitates internal dosimetry calculations for offspring. We parameterized the model for mice, rats, and humans using time-varying functions for body mass and milk consumption rates. The only required substance-specific parameter is the elimination half-life of the LPEC in the animal species of interest. We used the model to estimate whole-body concentrations in mothers and offspring following maternal exposures to hexachlorobenzene (HCB) and 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB 153) and compared these with measured concentrations from animal studies. We also compared estimated concentrations for humans to those generated using a previously published human LPEC PK model. Finally, we compared human equivalent doses (HEDs) calculated using our model and an allometric scaling method. Estimated and observed whole-body concentrations of HCB and PCB 153 in offspring followed similar trends and differed by less than 60%. Simulations of human exposure yielded concentration estimates comparable to those generated using the previously published model, with concentrations in offspring differing by less than 12%. HEDs calculated using our PK model were about 2 orders of magnitude lower than those generated using allometric scaling. Our PK model can be used to calculate internal dose metrics for offspring and corresponding HEDs and thus informs assessment of developmental toxicity risks associated with LPECs.
Biomonitoring studies have shown that pregnant women living in regions of unconventional natural gas (UNG) exploitation have higher levels of trace elements. Whether developmental endocrine ...disruption can be expected at these exposure levels during pregnancy is unclear. In this study, we aimed to test the impact of five trace elements alone or in mixtures using in vitro cell- and tissue-based assays relevant to endocrine disruption and development. Manganese, aluminum, strontium, barium, and cobalt were tested at concentrations including those representatives of human fetal exposure. Using transactivation assays, none of the tested elements nor their mixture altered the human estrogen receptor 1 or androgen receptor genomic signalling. In the rat fetal testis assay, an organ culture system, cobalt (5 μg/l), barium (500 μg/l) and strontium (500 μg/l) significantly increased testosterone secretion. Cobalt and strontium were associated with hyperplasia and/or hypertrophy of fetal Leydig cells. Mixing the five elements at concentrations where none had an effect individually stimulated testosterone secretion by the rat fetal testis paralleled by the significant increase of 3β-hydroxysteroid dehydrogenase protein level in comparison to the vehicle control. The mechanisms involved may be specific to the fetal testis as no effect was observed in the steroidogenic H295R cells. Our data suggest that some trace elements in mixture at concentrations representative of human fetal exposure can impact testis development and function. This study highlights the potential risk posed by UNG operations, especially for the most vulnerable populations, pregnant individuals, and their fetus.
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•Trace elements were tested at levels relevant to human fetal exposure.•Cobalt, barium and strontium increased rat fetal testicular testosterone secretion.•Mixture of 5 trace elements increased rat fetal testicular testosterone secretion.•Trace elements disrupted fetal Leydig cells and a steroidogenesis enzyme expression.•The disruptive effect of trace elements is specific to the fetal testis.
Abstract Northeastern British Columbia is a region of prolific unconventional oil and gas (UOG) activity. UOG activity can release volatile organic compounds (VOCs) which can elevate oxidative stress ...and disrupt antioxidant activity in exposed pregnant individuals, potentially increasing the risk of adverse pregnancy outcomes. This study measured biomarkers of oxidative stress and antioxidant activity in pooled urine samples of 85 pregnant individuals living in Northeastern British Columbia, to analyze associations between indoor air VOCs, oil and gas well density and proximity metrics, and biomarker concentrations. Concentrations of catalase, superoxide dismutase (SOD), glutathione S-transferase, total antioxidant capacity, 6-hydroxymelatonin sulfate (aMT6s), malondialdehyde (MDA), 8-hydroxy-2′-deoxyguanosine (8-OHdG), and 8-isoprostane were measured using assay kits. Associations between exposure metrics and biomarker concentrations were determined using multiple linear regression models adjusted for biomarker-specific covariables. UOG proximity was associated with decreased SOD and 8-OHdG. Decreased 8-OHdG was associated with increased proximity to all wells. Decreased aMT6s were observed with increased indoor air hexanal concentrations. MDA was negatively associated with indoor air 1,4-dioxane concentrations. No statistically significant associations were found between other biomarkers and exposure metrics. Although some associations linked oil and gas activity to altered oxidative stress and antioxidant activity, the possibility of chance findings due to the large number of tests cannot be discounted. This study shows that living near UOG wells may alter oxidative stress and antioxidant activity in pregnant individuals. More research is needed to elucidate underlying mechanisms and to what degree UOG activity affects oxidative stress and antioxidant activity.
An association between serum levels of two perfluoroalkyl substances (PFAS) and delayed age at menarche was reported in a cross-sectional study of adolescents. Because perfluorooctanoic acid (PFOA) ...and perfluorooctane sulfonate (PFOS) have half-lives of years, growth dilution and the development of a new route of excretion (menstruation) could account for some or all of the reported association.
To assess how much of the epidemiologic association between PFAS and delayed menarche can be explained by the correlation of growth and maturation with PFAS body burden.
We developed a Monte Carlo (MC) physiologically-based pharmacokinetic (PBPK) model of PFAS to simulate plasma PFAS levels in a hypothetical female population aged 2 to 20years old. Realistic distributions of physiological parameters as well as timing of growth spurts and menarche were incorporated in the model. The association between PFAS level and delayed menarche in the simulated data was compared with the reported association.
The prevalence of menarche, distributions of age-dependent physiological parameters, and quartiles of serum PFAS concentrations in the simulated subjects were comparable to those reported in the epidemiologic study. The delay of menarche in days per natural log increase in PFAS concentrations in the simulated data were about one third as large as the observed values.
The reported relationship between PFAS and age at menarche appears to be at least partly explained by pharmacokinetics rather than a toxic effect of these substances.
•Ability to simulate longitudinal trends in blood biomarkers in early life•Kinetic variation contributed to the association between PFAS and age at menarche.•MC-PBPK modeling can enhance interpretation of epidemiological associations.
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