Arsenic Speciation and Metallomics Profiling of Human Toenails as a Biomarker to Assess Prostate Cancer Cases: Atlantic PATH Cohort Study

Abstract

Chronic exposure to inorganic arsenic and trace metals has been linked to prostate cancer, and altered arsenic methylation capacity may have an important role in arsenic carcinogenesis. Biomarkers may be able to elucidate this role. Our objectives were to characterize profiles of arsenic species and metallome in toenails and urine samples, compare profiles between prostate cancer cases and controls, and determine the discriminant ability of toenail and urine biomarkers. Toenail samples (n = 576), urine samples (n = 152), and questionnaire data were sourced from the Atlantic Partnership for Tomorrow's Health (PATH) cohort study. Healthy controls were matched to prostate cancer cases (3:1 ratio) on sex, age, smoking status, and the province of residence. Metallome profiles and proportions of arsenic species were measured in toenail and urine samples. Analysis of covariance (ANCOVA) was used to compare the mean percent monomethylarsonic acid (%MMA), dimethylarsonic acid (%DMA), inorganic arsenic (%iAs), primary methylation index (PMI, MMA/iAs), and secondary methylation index (SMI, DMA/MMA). Multivariate analysis of covariance (MANCOVA) was used to compare selected metal concentrations. Mean %MMA was significantly lower and SMI was significantly higher in toenails from prostate cancer cases compared to controls in unadjusted and adjusted models. Proportions of arsenic species were correlated with total arsenic in toenails. Arsenic speciation in urine was not different between cases and controls, nor were metallome profiles in toenails and urine. Our results indicate that toenails are a viable biomarker for altered arsenic speciation in prostate cancer cases and may have greater utility than urine in this context.

Toenail arsenic species and metallome profiles associated with breast, cervical, prostate, and skin cancer prevalence in the Atlantic Partnership for Tomorrow’s Health cohort

“…The method used to digest and analyze toenails has been previously described and validated ( 33 , 34 ). In brief, toenail samples were weighed to an approximate mass of 50 mg and transferred to a 10 mL quartz vial for cleaning.…”

“…This study expanded our previous work by characterizing the profiles of arsenic species and metallomes in human toenails from the Atlantic Partnership for Tomorrow’s Health (Atlantic PATH) cohort and focusing on less studied cancers (cervical, breast and prostate cancers), which have also been linked to arsenic exposure ( 33 , 34 ). Specifically, we aimed to assess the relationship between the profiles of arsenic species and metallomes and cancers, and determine the roles of these profiles in cancer cases ( 37 ).…”

“…There is increasing evidence to indicate that metal speciation plays an important role in toxicity, particularly in the case of arsenic ( 14 , 33 – 35 ). The use of urine biomarkers to measure arsenic species is useful to investigate potential associations using known methodologies; however, the use of more advanced techniques and long-term biomarkers (i.e., metallome and speciation analysis with toenails) may further our understanding of the link between chronic heavy metal exposure, arsenic speciation, and cancer.…”

Metal Profiles in Autism Spectrum Disorders: A Crosstalk between Toxic and Essential Metals

“…It is well recognized that the brain and fetus are particularly prone to toxic organometallic species, including organic derivatives of Hg, Pb, and As [168,169]. Therefore, speciation analysis is a precious source of helpful information in studying various pathologies [170][171][172]. Unfortunately, very little is known about metal speciation in ASD, and the detailed description of the molecular mechanisms of single-species toxicity in ASD remains largely unknown.…”

Urine Self-Sampling Kit Combined with an Automated Preparation-Sampler Device for Convenient and Reliable Analysis of Arsenic Metabolites by HPLC–ICPMS

“…The collected urine samples usually undergo a series of operations such as extraction, filtration, metabolite separation, and detection, during which urine exposure to air or improper personnel operations will have a significant impact on the detection of unstable trivalent arsenic metabolites. , Automation provides a way to reduce human intervention in such processes. A number of automated/semiautomated methods such as flow injection and magnetic solid phase extraction coupled with high-performance liquid chromatography–inductively coupled plasma mass spectrometry (HPLC–ICPMS) have been successfully implemented for the speciation analysis of metals in drugs, seawater, or urine. , However, these methods still require manual sample transfer from the storage container to the preparation container, making it difficult to avoid sample exposure to air.…”