Extramural papers of the month
By Nancy Lamontagne
- Mechanism for melanoma risk in people with red hair and fair skin
- Early exposures to air pollution linked with autism
- Flame retardant Firemaster 550 confirmed as endocrine disruptor
- Prenatal mercury and ADHD
Mechanism for melanoma risk in people with red hair and fair skin
A study supported by the NIEHS identifies a new mechanism that helps explain risk for melanoma, the most dangerous type of skin cancer, and provides information that might aid in protecting people with the highest melanoma risk.
Pheomelanin, the predominant skin pigment for people with red hair and fair skin, is less protective against ultraviolet (UV) radiation damage than the eumelanin found in people with dark skin and hair. However, studies indicate that reduced UV protection may not fully explain why individuals with red hair and freckles are more at risk for melanoma, so the researchers conducted a study involving dark-colored mice with the typical gene variant for a predominance of eumelanin and mice with the variant that produces red hair and fair skin in humans.
Even without UV exposure, the red hair/fair skin mice had a greater number of invasive melanomas, suggesting that the pheomelanin pigment itself was involved in melanoma. The researchers then tested mice with no skin pigment (albino), and these mice developed fewer melanomas than the red hair/fair skin mice. In addition, the red hair/fair skin mice had significantly greater oxidative DNA and lipid damage than the albino mice. The study findings suggest that in the absence of UV exposure, the pheomelanin pigment contributes to melanoma via oxidative damage. The researchers say protection from ultraviolet radiation remains important, but additional strategies may be needed to achieve the best melanoma prevention.
Citation: Mitra D, Luo X, Morgan A, Wang J, Hoang MP, Lo J, Guerrero CR, Lennerz JK, Mihm MC, Wargo JA, Robinson KC, Devi SP, Vanover JC, D'Orazio JA, McMahon M, Bosenberg MW, Haigis KM, Haber DA, Wang Y, Fisher DE. 2012. An ultraviolet-radiation-independent pathway to melanoma carcinogenesis in the red hair/fair skin background. Nature 491(7424):449-453.
Early exposures to air pollution linked with autism
NIEHS grantees report that exposure to local traffic-related air pollution and regional air pollution in the womb and during the first year of life is associated with increased risk for autism. The study builds on previous research in which the grantees found that children born to mothers who live within 309 meters of freeways had an increased risk of developing autism.
In the new study, the researchers examined data from children enrolled in the Childhood Autism Risks from Genetics and the Environment study, including 279 children with autism and 245 control children with normal development. They estimated traffic-related pollution exposures using the mother’s address and used U.S. Environmental Protection Agency’s Air Quality System measurements of regional pollution.
The children with autism were more likely than the control children to live in homes with the highest exposure to traffic-related air pollution during gestation (adjusted odds ratio [AOR] 1.98 [95 percent confidence interval (CI) 1.20-3.31]) and the first year of life (AOR, 3.10 [95 percent CI, 1.76-5.57]). During gestation, exposure to regional nitrogen dioxide and particulate matter less than 2.5 and 10 microns in diameter was also associated with autism. The researchers say that additional population and toxicological studies of likely biological pathways are needed to determine if the air pollution exposure causes the increase in autism risk.
Citation: Volk HE, Lurmann F, Penfold B, Hertz-Picciotto I, McConnell R. 2012. Traffic-Related Air Pollution, Particulate Matter, and Autism. Arch Gen Psychiatry; doi:10.1001/jamapsychiatry.2013.266 [Online 26 November 2012].
Flame retardant Firemaster 550 confirmed as endocrine disruptor
The flame-retardant mixture Firemaster 550 is commonly found in household dust, but the physiological effects of its components at relevant exposure levels aren’t known. An animal study conducted by NIEHS grantees shows that perinatal exposure to the flame-retardant mixture is associated with endocrine disrupting effects. The researchers observed weight gain, early onset of puberty, and cardiovascular health effects at levels that are relevant to human exposure and lower than the no observable adverse effects level reported by the manufacturer.
The researchers evaluated the effects of FM 550 in rats exposed to 100 or 1000 micrograms of the flame-retardant per day during gestation and lactation. They found that the components of Firemaster 550 accumulated in tissues of exposed mice as well as their offspring and induced metabolic syndrome characteristics in the offspring. They observed higher levels of the thyroxine thyroid hormone and reduced hepatic carboxylesterease activity in the exposed mice. The offspring exhibited advanced female puberty, weight gain, male cardiac hypertrophy, and problems with exploratory behaviors. The researchers say that their findings reveal that the flame retardant may affect growth and neurodevelopment and support the need for more research into the mechanisms involved and human exposure levels.
Citation: Patisaul HB, Roberts SC, Mabrey N, McCaffrey KA, Gear RB, Braun J, Belcher SM, Stapleton HM. 2012. Accumulation and Endocrine Disrupting Effects of the Flame Retardant Mixture Firemaster(®) 550 in Rats: An Exploratory Assessment. J Biochem Mol Toxicol; doi: 10.1002/jbt.21439 [Online 8 November 2012].
Prenatal mercury and ADHD
A new paper from NIEHS-funded researchers found an association between low-level prenatal mercury exposure and increased risk of attention-deficit/hyperactivity disorder (ADHD)-related behaviors in children. However, consuming more than two serving of fish per week was linked with a lower risk for ADHD-related behaviors.
The researchers studied children born in New Bedford, Mass. They conducted neuropsychological assessments for children at age 8 who had peripartum maternal hair mercury measures (421 children) or maternal reporting of fish consumption during pregnancy (515 children). The mothers’ median hair mercury level was 0.45 micrograms per gram (mg/g) (range = 0.03 to 5.14 mg/g), and 52 percent of them consumed more than two servings of fish a week. Multivariable regression models showed that mercury exposure was associated with inattention and impulsivity/hyperactivity. Associations between mercury and behavior were detected primarily for boys. However, when the mothers consumed more than two servings of fish per week, there was a protective effect for ADHD-related behaviors, particularly impulsive/hyperactive behaviors (relative risk = 0.4; 95 percent CI 0.2-0.6).
The author of a related editorial said that the study’s findings point to the need for a national scientific advisory panel to evaluate environmental influences of ADHD and that new evidence linking environmental contaminants with ADHD reinforces the urgency of revising the regulatory framework for environmental contaminants and toxicants.
Citation: Sagiv SK, Thurston SW, Bellinger DC, Amarasiriwardena C, Korrick SA. 2012. Prenatal Exposure to Mercury and Fish Consumption During Pregnancy and Attention-Deficit/Hyperactivity Disorder–Related Behavior in Children. Arch Pediatr Adolesc Med 166(12):1123-1131. Related Editorial: Lanphear BP. 2012. Attention-Deficit/Hyperactivity Disorder: A Preventable Epidemic? Arch Pediatr Adolesc Med 166(12):1182-1184.
(Nancy Lamontagne is a science writer with MDB, Inc., a contractor for the NIEHS Division of Extramural Research and Training, Superfund Research Program, and Worker Education and Training Program.)