Papers of the Month
By Sara Amolegbe
Flame retardant linked to hyperthyroidism in cats
Feline hyperthyroidism is associated with exposure to flame retardant chemicals found in household items, such as textiles and polyurethane foam, according to an NIEHS-funded study. Feline hyperthyroidism is the most commonly diagnosed endocrine-related disease among senior and geriatric housecats.
The researchers recruited owners of 78 housecats seven years and older with and without feline hyperthyroidism. The cats wore pet tags made of silicone, which pick up a variety of contaminants in the air, for seven days. The research team previously used similar silicone samplers, in the form of wristbands, to monitor human exposure to environmental chemicals.
When they analyzed the silicone for flame retardant chemicals, the scientists found higher levels of the flame retardant tris(1,3-dichloroisopropyl) phosphate (TDCIPP) in the cats with hyperthyroidism. Among non-hyperthyroid cats, higher TDCIPP levels from the silicone tags were associated with higher blood levels of a hormone elevated in hyperthyroidism, indicating that they might be more likely to develop hyperthyroidism in the future. The higher TDCIPP exposures were linked to air freshener use, houses built since 2005, and cats that prefer to nap on upholstered furniture.
TDCIPP and other alternatives were introduced as flame retardants after polybrominated diphenyl ethers (PBDEs) were phased out in 2004 due to environmental and health concerns. Previous research suggested a link between PBDEs and feline hyperthyroidism, but this was the first study that focused on PBDE alternatives and feline hyperthyroidism and suggested that TDCIPP might have similar health effects.
Citation: Poutasse CM, Herbstman JB, Peterson ME, Gordon J, Soboroff PH, Holmes D, Gonzalez D, Tidwell LG, Anderson KA. 2019. Silicone pet tags associate tris(1,3-dichloro-2-isopropyl) phosphate exposures with feline hyperthyroidism. Environ Sci Technol 53(15):9203–9213.
Molecule senses DNA damage and supervises repair
A team of NIEHS grantees working wtih an NIEHS in-house researcher found that a protein that helps safeguard against DNA damage from the sun is also useful for finding general DNA damage and overseeing its repair. The protein, ultraviolet-damaged DNA-binding protein (UV-DDB), is a known key protein in human global nucleotide excision repair, which is an important mechanism for removing DNA damage caused by UV light. This study showed that the protein also senses damage and plays a key role in base excision repair, another important DNA repair pathway.
The research team developed a new method to track enzymes involved in DNA repair in 3D using real-time, single molecule imaging. They induced oxidative stress in DNA and observed that UV-DDB was rapidly recruited to sites containing specific DNA damage. UV-DDB also stimulated repair activity by forming complexes with enzymes that are essential in base excision repair. One important rate-limiting step during base excision repair is access to DNA damage in tightly packed chromatin in the nucleus. They found that UV-DDB can find damage on DNA buried in chromosomes and help DNA repair molecules access those sites.
To further explore the role of UV-DDB in base excision repair, researchers depleted UV-DDB from living cells and compared them to cells with UV-DDB. When they inflicted damage usually repaired by base excision on both types of cells, they found that loss of UV-DDB sensitized cells to the DNA damage. According to the authors, this study provides novel insight into a new damage sensor role for UV-DDB in base excision repair.
Citation: Jang S, Kumar N, Beckwitt EC, Kong M, Fouquerel E, Rapic-Otrin V, Prasad R, Watkins SC, Khuu C, Majumdar C, David SS, Wilson SH, Bruchez MP, Opresko PL, Van Houten B. 2019. Damage sensor role of UV-DDB during base excision repair. Nat Struct Mol Biol 26(8):695–703. (Story)
Collaborative Cross mice reveal different susceptibilities
NIEHS grantees found that the Collaborative Cross (CC) mouse model — which uses genetically diverse mice to capture over 90% of the known mouse genetic variations — can account for individual differences in susceptibility to environmental chemicals. Using the CC mouse model, researchers measured individual variability in kidney toxicity after exposure to tetrachloroethylene (PERC), a solvent frequently used in dry cleaning solutions, adhesives, and metal degreasers.
Overall, mice exposed to PERC had lower kidney weight and more markers of kidney injury, supporting previous findings that the kidney is a target of PERC toxicity. Among the 45 CC strains tested, the team found variation in PERC metabolism and toxicity, with greater variability observed in levels of toxicity than in metabolism. They also found that inbred mice used in previous studies generally exhibited metabolism of PERC at the lower end of the overall distribution. Because differences in metabolism can affect how quickly toxicants leave the body, lower metabolism of PERC may indicate that those inbred strains may underestimate effects in a more general population.
According to the authors, when comparing the results of this study to the default values that are generally used by the U.S. Environmental Protection Agency in human health risk assessments to adjust for population variation, the default values may protect 95% of the population but not the most sensitive individuals. This study illustrates how the CC mouse population can be used to fine-tune protective adjustment factors for population variability in risk assessments.
Citation: Luo YS, Cichocki JA, Hsieh NH, Lewis L, Wright FA, Threadgill DW, Chiu WA, Rusyn I. 2019. Using collaborative cross mouse population to fill data gaps in risk assessment: a case study of population-based analysis of toxicokinetics and kidney toxicodynamics of tetrachloroethylene. Environ Health Perspect 127(6):67011.
Organic diet reduces pesticide metabolites in pregnant women
Switching to organic produce during pregnancy can reduce markers of pesticide exposure, according to an NIEHS-funded study. Higher prenatal exposures to pyrethroid pesticides have been previously linked to poorer neurological and cognitive development in children.
Researchers conducted the first known long-term diet intervention study on the effects of organic produce in pregnant women. The researchers studied 20 pregnant women for six months during their second and third trimesters. One group was given weekly deliveries of organic produce. The other received conventional produce. The women completed a food diary and provided weekly urine samples.
Food diary data demonstrated that 66% of all servings of fruits and vegetables consumed by participants in the organic produce group were organic, compared to less than 3% in the conventional produce group. The women who consumed organic produce had significantly lower pyrethroid pesticide metabolites in their urine. The researchers did not observe significant differences for markers of organophosphate pesticide exposure.
According to the authors, the study demonstrates that it is not necessary to consume a fully organic diet to significantly reduce pyrethroid pesticide exposure. Participants reduced their exposure by consuming organic food as part of their diet rather than their whole diet, more like the way many people usually consume organic food.
Citation: Curl CL, Porter J, Penwell I, Phinney R, Ospina M, Calafat AM. 2019. Effect of a 24-week randomized trial of an organic produce intervention on pyrethroid and organophosphate pesticide exposure among pregnant women. Environ Int; doi:10.1016/j.envint.2019.104957 [Online 16 July 2019].
(Sara Amolegbe is a research and communication specialist for MDB Inc., a contractor for the NIEHS Division of Extramural Research and Training.)