Papers of the Month
By Sara Amolegbe
Maternal DDT exposure linked to autism risk
Mothers with high levels of the pesticide DDT in their blood during pregnancy are more likely to bear children who develop autism, according to an NIEHS-funded study. The study was the first to connect DDT with autism using a direct measure of exposure in maternal blood.
The researchers measured levels of DDT and polychlorinated biphenyl (PCB) metabolites in blood samples collected during the Finnish Prenatal Study of Autism. The study involved more than a million women and children born between 1987 and 2005 in Finland. The scientists compared 778 children diagnosed with autism, and their mothers, to 778 child-mother pairs without an autism diagnosis. The children with and without autism were matched for date of birth, sex, and place of residence.
The analysis revealed that mothers with DDT metabolite levels in their blood in the highest 25th percentile were 32 percent more likely than women with lower DDT levels to give birth to children who developed autism. The likelihood of having a child with autism accompanied by intellectual disability was twice as high in mothers with elevated DDT levels compared with those with lower levels. They found no association between PCB metabolites and autism.
The researchers offered two possible explanations for their observation that maternal exposure to DDT was related to autism but maternal PCB exposure was not. Low birth weight and premature birth, which are known risk factors for autism, have both been previously linked to maternal exposure to DDT, but not to PCBs. Maternal DDT exposure has also been shown to inhibit androgen receptor binding, which is a key process to neurodevelopment.
Citation: Brown AS, Cheslack-Postava K, Rantakokko P, Kiviranta H, Hinkka-Yli-Salomaki S, McKeague IW, Surcel HM, Sourander A. 2018. Association of maternal insecticide levels with autism in offspring from a national birth cohort. Am J Psychiatry doi: 10.1176/appi.ajp.2018.17101129. [Online 16 Aug 2018].
Arsenic influences gut microbiome of male infants
NIEHS grantees reported that arsenic in drinking water from private wells in New Hampshire was associated with significant effects on the gut microbiome of male, but not female, infants. The effect was strongest in babies who were not exclusively breast fed.
In 204 6-week-old infants from the New Hampshire Birth Cohort Study, researchers analyzed urinary arsenic, the overall microbiome community composition, and bacterial taxa critical for immune training in infancy. Well water used by the mothers in the cohort exhibited total arsenic concentrations ranging from below the limit of detection to 57 micrograms per liter. Only 2 percent of wells exceeded the U.S. Environmental Protection Agency maximum contaminant level of 10 micrograms per liter.
The researchers found associations with overall microbiome community composition among formula-fed males but not among breastfed infants or formula-fed females. Exclusively breastfed babies also had lower urinary arsenic concentrations than formula- or mixed-fed infants in the cohort.
According to the authors, this was the first study to look at the association between infant arsenic exposure and gut microbiome composition in the U.S. Previous studies examined associations in mice and researched the effects on the gut microbiome composition in children in areas of the world with higher levels of arsenic contamination in drinking water.
Citation: Hoen AG, Madan JC, Li Z, Coker M, Lundgren SN, Morrison HG, Palys T, Jackson BP, Sogin ML, Cottingham KL, Karagas MR. 2018. Sex-specific associations of infants' gut microbiome with arsenic exposure in a US population. Sci Rep 8(1):12627.
Hexavalent chromium induces permanent and heritable cell changes
NIEHS grantees showed that exposure to hexavalent chromium can lead to changes to genetic information in human lung cells. Hexavalent chromium is a known lung carcinogen, but the mechanism by which it causes cancer is not well understood. In human lung cells exposed to hexavalent chromium, the researchers observed permanent and heritable changes in DNA molecules that carry genetic information, known as chromosomes, as well as problems in DNA repair.
The researchers exposed lung cells to hexavalent chromium for three 24-hour periods, each about a month apart. After each treatment, they seeded cells onto new plates to regrow. Each generation of cells was tested for changes to chromosomes and DNA repair capacity.
The study provided evidence for the first time that hexavalent chromium induced chromosome translocations, or abnormal arrangements of chromosomes. They also found that exposure to hexavalent chromium inhibited DNA repair. Both the chromosome translocations and the DNA repair inhibition persisted after exposure ceased and both were heritable at the cellular level.
According to the authors, these chromosome imbalances likely lead to preferential selection and survival of abnormal cells, which may provide a growth advantage for cancer cells.
Citation: Wise SS, Aboueissa AE, Martino J, Wise JP Sr. 2018. Hexavalent chromium-induced chromosome instability drives permanent and heritable numerical and structural changes and a DNA repair-deficient phenotype. Cancer Res 78(15):4203−4214.
Bone lead linked to glaucoma
Higher bone lead levels are associated with an increased risk of primary open-angle glaucoma (POAG) according to an NIEHS-funded study. POAG is the most common form of glaucoma, affecting about three million Americans.
The 634 POAG-free men examined by the researchers had lead measurements taken from their patella and tibia bones between January 1991 and December 1999, and underwent standard evaluations by optometrists until December 2014. The researchers identified 44 cases of POAG by the end of follow-up. They found that men with the top half of patella lead levels had a more than three times higher risk of developing POAG compared with those in the lowest quartile of lead levels during the 15 years of follow-up. A ten-fold increase in patella lead level was associated with a more than a five-fold higher risk of POAG during the same time period. Similar, but slightly weaker, associations were observed for lead found in the tibia.
The study provided evidence that lead found in bone might be an important risk factor for POAG in a U.S. population of men. According to the authors, the findings contributed additional evidence of long-term health effects from environmental lead exposure, which might help strengthen public awareness of lead-related ocular diseases.
Citation: Wang W, Moroi S, Bakulski K, Mukherjee B, Weisskopf MG, Schaumberg D, Sparrow D, Vokonas PS, Hu H, Park SK. 2018. Bone lead levels and risk of incident primary open-angle glaucoma: The VA Normative Aging Study. Environ Health Perspect 126(8):087002.