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Intramural Papers of the Month

By Robin Arnette
November 2008

Compact Fluorescent Light Bulbs Are Safe Substitutes for Standard Incandescent Bulbs

NIEHS scientists have determined that energy-saving compact fluorescent light (CFL) bulbs should not aggravate skin rashes in people with skin disorders, as an earlier report had claimed. The NIH-funded research suggests that CFL bulbs are safe* and can be substituted for standard incandescent bulbs.

A February 3, 2008 article in Parade magazine titled "Bright Lights, Bad Headache?" stated that CFLs "can aggravate skin rashes in people with lupus, eczema, dermatitis or porphyria." The research team addressed the concern by calculating the potential photosensitization indices of protoporphyrin IX — a typical porphyrin that is present in the skin of porphyria patients — and riboflavin — a putative lens phototoxin — versus a 14 W CFL bulb, a 60 W soft white incandescent (SWIL) bulb and two 40 W cool white fluorescent (CWF) bulbs. High values would have indicated a greater possibility for photosensitization of the skin or eyes. The results indicated that a 14 W CFL bulb, which is comparable to a 60 W SWIL bulb, actually had a photosensitization index that was half of that for a 60 W SWIL bulb.

The team also compared the emission spectra of the three types of bulbs. The results indicated that while all three bulbs emitted low UVB, only the CFL and CWL bulbs emitted UVA. In addition, both CFL and CWL bulbs displayed similar emission spectra values. Taken together, the findings suggest that CFL bulbs will not increase the phototoxicity of porphyrins or riboflavin and are safe for people with skin irritations.

*This safety assessment relates only to the quality of light regarding its photosensitizing potential and does not consider the presence of mercury in fluorescent light bulbs, which may create a safety problem during lamp breakage.

Citation: Chignell CF, Sik RH, Bilski PJ ( NIEHS. 2008. The photosensitizing potential of compact fluorescent vs. incandescent light bulbs. Photochem Photobiol 84(5):1291-1293.

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Cadmium Produces Free Radicals in Rats

The environmental and industrial pollutant cadmium (Cd) induces the in vivo generation of free radicals in murine liver cells, according to researchers from NIEHS. This work is the first to demonstrate that Cd-induced radical formation is dependent on the activation of Kupffer cells, liver macrophages and iron-catalyzed reactions.

Prior to this study, numerous journal articles had indicated that metals like Cd affected signaling pathways and produced radicals that caused DNA damage, altered gene expression, apoptosis and the oxidation of lipids and proteins, but no direct evidence had been reported. The research team used electron spin resonance (ESR) spectroscopy to examine which adducts were produced in rats following the administration of cadmium chloride (CdCl2) and the spin trapping agent α-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN).

Depletion of hepatic glutathione by diethyl maleate significantly increased free radical production, whereas inactivation of Kupffer cells by gadolinium chloride and chelation of iron by desferal inhibited it. Treatment with the xanthine oxidase inhibitor allopurinol, the catalase inhibitor aminobenzotriazole or the cytochrome P-450 inhibitor 3-amino-1, 2, 4-triazol had no effect. This is the first study to show Cd generation of reactive oxygen- and carbon-centered radical species by involvement of both iron mediation through iron-catalyzed reactions and activation of Kupffer cells, the resident liver macrophages.

Citation: Liu J, Qian SY, Guo Q, Jiang J, Waalkes MP, Mason RP, Kadiiska MB ( NIEHS. 2008. Cadmium generates reactive oxygen- and carbon-centered radical species in rats: Insights from in vivo spin-trapping studies. Free Radic Biol Med 45(4):475-481.

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The Case-Mother/Control-Mother Design Is Statistically Enhanced If We Account for Family Relationships

In research to identify the roles of genetic variants in young-onset conditions like birth defects and schizophrenia, there are two genomes to consider: that of the child and that of the mother. Epidemiologists can use a case-mother/control-mother design, where affected offspring and their mothers are genotyped, along with a control group of healthy offspring and their mothers. One then treats the mother-offspring pairs as the unit of analysis. Investigators from NIEHS and Radboud University in the Netherlands have shown that the statistical power of analyses based on this design can be improved by using models that impose some natural assumptions.

The simplest assumption is that transmissions from parent to child follow Mendelian laws; applying this insight brings substantial gains in power. One can additionally assume genetic symmetry between the mother and father, which provides still more power. A third assumption, involving "allelic exchangeability," confers additional gains.

Although an extra individual must be genotyped for every case under a case-mother/control-mother design — with equal numbers of case and control pairs — compared with a case-parent-triad design, for some risk scenarios the imposition of assumptions based on the family relationships can render the case-mother/control-mother design more powerful than a case-parent triads design.

Citation: Shi M, Umbach DM, Vermeulen SH, Weinberg CR ( NIEHS. 2008. Making the most of case-mother/control-mother studies. Am J Epidemiol 168(5):541-547.

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Double-Strand Breaks Can Reconfigure Genome

Researchers from NIEHS, Duke University and Universidade Estadual de Campinas in Brazil report that DNA double-strand breaks (DSBs) that occur in repetitive elements of the genome of the budding yeast Saccharomyces cerevisiae often result in chromosome aberrations (CAs) that can reconfigure the genome. The authors believe that this reshaping of an organism's genome may drive evolutionary change.

The investigators used ionizing radiation to induce ~250 DSBs per diploid G2 cell and found that although the vast majority of breaks were repaired efficiently and accurately by homologous recombination (HR) between sister chromatids, multiple CAs among survivor colonies were frequent. CAs were initially identified using pulsed-field gel electrophoresis and then analyzed using comparative genome hybridization (CGH) to identify the breakpoints of rearranged chromosomes. Nearly all of the CAs resulted from HR between nonallelic repetitive elements, mainly Ty retrotransposons.

This study provides a possible mechanism for disease-associated CAs that may arise in humans and lends credence to the theory that HR between repetitive DNA is a source of genomic variation in humans.

Argueso JL, Westemoreland J, Mieczkowski PA, Gawel M, Petes TD, Resnick MA ( NIEHS. 2008. Double-strand breaks associated with repetitive DNA can reshape the genome. Proc Natl Acad Sci USA 105(33):11845-11850.

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