Associations of children's urinary metals with blood RNA N⁶-methyladenosine and 2'-O-methyladenosine

Post-transcriptional RNA modifications (the epitranscriptome) regulate gene expression and represent a pathway through which environmental exposures can affect health. Two RNA modifications important for health and disease are N⁶-methyladenosine (m⁶A) and 2'-O-methyladenosine (Am). However, the effects of metals and metalloids (hence, metals), on m⁶A and Am are less well understood. We aimed to investigate associations between children's metals exposures and global m⁶A and Am in blood.

We measured essential (cobalt, copper, selenium, zinc) and nonessential (arsenic, cadmium, chromium, cesium, mercury, antimony) metals in urine and total m⁶A and Am in blood using liquid chromatography-tandem mass spectrometry in 150 children aged 9-11 in the Mexico City Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) cohort. We determined cross-sectional associations of log₂-transformed metals mixtures with m⁶A and Am using quantile g-computation and linear regression.

Median m⁶A (expressed as %m⁶A/A) was 0.075 (interquartile range [IQR] 0.069, 0.079); median Am (%Am/A) was 2.53 (IQR 2.44, 2.66). Each quartile increase in the overall metal mixture was associated with a decrease of -0.095 (95 % confidence interval [CI] -0.15, -0.044) in %Am/A, adjusted for other metals, sex, age, visit date, and total RNA concentration. Each doubling of arsenic was associated with a decrease of -0.047 (-0.089, -0.0056) and each doubling in cesium was associated with a decrease of -0.096 (-0.18, -0.015) in %Am/A.

Exposure to nonessential metals may be related to global Am levels in children. Further research is warranted to evaluate potential roles of Am and m⁶A in metal-induced toxicity.