Papers of the Month
By Nancy Lamontagne
Smoking tobacco and burning smoky coal elicit similar gene expression patterns
A study, funded in part by NIEHS, showed that nonsmoking women in rural China who burned smoky, or bituminous, coal for heating and cooking exhibited certain gene expression patterns similar to those of active cigarette smokers. These results shed new light on the molecular mechanisms associated with smoky coal exposure, and may eventually lead to the development of clinical biomarkers that could help detect or assess the risk of lung cancer in people exposed to smoky coal.
The high rate of lung cancer in some rural counties in China has been linked to burning smoky coal. To better understand the molecular changes associated with exposure, the researchers conducted gene-expression profiling of cheek cells acquired from healthy, nonsmoking females in China, 26 of whom burned smoky coal and nine who used smokeless anthracite coal.
The researchers identified 282 genes that expressed differently in women exposed to smoky coal, compared to the smokeless coal. These gene expression changes correlated with household levels of fine particulate matter and polycyclic aromatic hydrocarbons. Some of the gene expression changes observed in the women exposed to smoky coal were similar to those found in cigarette smokers, suggesting that tobacco smoke and smoky coal exposure elicit a similar molecular response in the cells of the airway.
Citation: Wang TW, Vermeulen RC, Hu W, Liu G, Xiao X, Alekseyev Y, Xu J, Reiss B, Steiling K, Downward GS, Silverman DT, Wei F, Wu G, Li J, Lenburg ME, Rothman N, Spira A, Lan Q. 2015. Gene-expression profiling of buccal epithelium among non-smoking women exposed to household air pollution from smoky coal. Carcinogenesis. 36(12):1494-1501.
Analyzing nanoparticle-induced oxidative stress
An NIEHS grantee and colleagues have developed an analytic approach known as quantitative redox proteomics that can detect how nanoparticles affect macrophages, which are immune cells that engulf and digest foreign particles, long before these cells die. Using this method, they found that even nanoparticles considered nontoxic can cause macrophages to experience some oxidative stress.
Many approaches to studying nanoparticle toxicity examine whether the particles cause cell death. The new approach provides more specific information, by detecting a protein modification known as S-glutathionylation. This modification, which occurs when a cell is under oxidative stress, is known to be involved in immune function. Using the new analysis technique, the researchers examined macrophages after exposure to silicon oxide, iron oxide, and cobalt oxide. These commercial nanoparticles vary in their potential to cause oxidative stress and cell death.
All three types of nanoparticles caused an increase in S-glutathionylation. However, the specific pattern of modification varied for each type of nanoparticle. By closely examining these modifications, the researchers identified specific molecular pathways that were most susceptible to low levels of oxidative stress, and distinguished those from pathways associated with oxidative stress levels high enough to cause cell death. These findings offer insight into pathways that may facilitate cellular adaption to nanoparticles versus pathways that link to irreversible cell damage.
Citation: Duan J, Kodali VK, Gaffrey MJ, Guo J, Chu RK, Camp DG, Smith RD, Thrall BD, Qian WJ. 2015. Quantitative profiling of protein s-glutathionylation reveals redox-dependent regulation of macrophage function during nanoparticle-induced oxidative stress. ACS Nano. 10(1):524-538.
Natural food additive prevents UV skin damage in mice
NIEHS grantees have discovered that a compound found in the natural food additive annatto prevents the formation of cancer cells and skin damage from ultraviolet (UV) radiation in mice. The compound prevents UV skin damage by inducing cells to make protective antioxidants and repair factors that prevent cancer cells from forming.
Annatto is often used as a yellow or orange food coloring and is consumed around the world. The researchers studied bixin, a bright reddish-orange compound found in annatto. After injecting a group of mice with bixin and exposing these mice and a control group to UV radiation, they found that the skin of mice receiving bixin experienced far less severe sun damage than the skin of the control mice. Because studies had suggested that nuclear factor-E2-related factor 2 (NRF2) could play a role in protecting cells from sun damage, the researchers also examined bixin’s protective effects in mice with and without NRF2. Bixin only showed its protective effects in the mice expressing NRF2, confirming that bixin-based cell protection is dependent on NRF2.
Experiments with cultured human skin cells also showed that bixin activates a NRF2-dependent protective response in cells. Since annatto is approved by the Food and Drug Administration as a safe food additive, the researchers suggested that future clinical trials necessary to test bixin may require fewer rounds of testing.
Citation: Tao S, Park SL, de la Vega MR, Zhang DD, Wondrak GT. 2015. Systemic administration of the apocarotenoid bixin protects skin against solar UV-induced damage through activation of NRF2. Free Radic Biol Med. 89:690-700.
Polycyclic aromatic hydrocarbon exposure and breast cancer
The likelihood of a relationship between polycyclic aromatic hydrocarbons (PAHs) from vehicular traffic and the incidence of breast cancer has been strengthened by new research funded in part by NIEHS. The study reported an association between comparatively high long-term exposure to traffic-related PAHs and breast cancer incidence in women, particularly women who consumed low amounts of fruit and vegetables or had hormone receptor-negative tumors.
The researchers assessed residential histories of 1,508 study participants with breast cancer and 1,556 participants with no breast cancer, in a population-based study conducted in 1996 and 1997. They reconstructed 1960-1995 traffic exposure estimates of benzo[a]pyrene, a PAH, using a historical, geographic exposure model that was consistent with various environmental measurements. Benzo[a]pyrene is often used as a marker of total PAH exposure.
The study showed that women with the highest exposures to traffic-related benzo[a]pyrene from 1960-1990 had a modestly higher chance of developing breast cancer than women with lower amounts of exposure (odds ratio of 2.68 compared to 0.78, respectively). The association remained when the researchers looked at just 1995 traffic exposure, with a stronger association among women with low fruit and vegetable intake. Compared to women without breast cancer, the association between breast cancer and traffic-related benzo[a]pyrene exposure was also stronger for women with estrogen/progesterone-negative tumors, but lower among all other tumor subtypes.
Although more studies are needed, the new results point to subgroups of women who potentially have greater susceptibility to breast cancer.
Citation: Mordukhovich I, Beyea J, Herring AH, Hatch M, Stellman SD, Teitelbaum SL, Richardson DB, Millikan RC, Engel LS, Shantakumar S, Steck SE, Neugut AI, Rossner P, Santella RM, Gammon MD. 2016. Vehicular traffic-related polycyclic aromatic hydrocarbon exposure and breast cancer incidence: the Long Island Breast Cancer Study Project (LIBCSP). Environ Health Perspect. 124(1):30-38.