Gender-specific protective effect of hemoglobin on arsenic-induced skin lesions David C. Christiani,MD,MPH,MS Dhaka, Bangladesh January 4, 2006
Harvard-DCH Collaborators • Carrie V. Breton, Andres Houseman, Molly Kile, Quazi Quamruzzaman, Mahmuder Rahman, Golam Mahiuddin, David C. Christiani. • Dhaka Community Hospital, Dhaka, Bangladesh and Harvard School of Public Health, Boston, Mass., USA
Background • Chronic arsenic poisoning is a major health concern in Bangladesh and in other regions of the world. • Mechanisms of human toxicity remain elusive, especially dermatologic outcomes. • In vitro and in vivo studies show that inorganic arsenic binds to hemoglobin and can change cell morphology, heme metabolism, and hemoglobin levels.
Background • Acute exposure to arsernite has been shown to cause anemia, leukopenia, and throbocytopenia from bone marrow suppression. • Arsine gas can cause hemolytic anemia. • Arsenic-induced skin lesions, cancerous lesions, have less hemoglobin than do non-cancerous lesions.
Background • Chronic arsenic ingestion alters heme metabolism and increases excretion of total porphyrins. • However, the effect of chronic As exposure on the hemologic system remains relatively unexplored, with no direct evidence of As related anemia.
Hemoglobin • Hemoglobin (Hgb) is of particular interest because of its use in the diagnosis of anemia. • Anemia is defined as a blood Hgb below 12g/dL. • Bangladesh: National prevalence of anemia has remained constant at 74% for the past 30 years. • Iron deficiency due to inadequate intake and low dietary bioavailability of iron.
Aims • To assess the relationship between blood Hgb and skin lesions in a case-control study of 1,800 persons in Pabna. • To assess potential interactions between AS, Hgb, and genetic polymorphisms in genes important for detoxification. • To examine direct associations between toenail and urinary arsenic levels and As in a disease-free, repeated measures study of 184 adults from 50 families is Pabna.
Methods • Case-Control Study:2001-2003, 900 case-control pairs (n=1,800) recruited • Physician-diagnosed lesions; keratosis, spotted melanosis, Bowen’s disease, SCC • Separate study: 248 persons (148 adults) from 50 families (25 in suspected high, 25 in suspected low exposure regions) for a four time per year sampling over 2001-2005. “Dosimetry Study”
Data collection and analysis • Hgb determined by Sahli’s method. • Toenail clippings- Total Inorganic As analyzed by ICP-MS. • Well-water sampling after several minute flush. • Blood for DNA – PCR for GSTM1, GSTT1, GSTP1.
Statistical Analysis • Descriptive statistics (Chi square, t-test,Wilcoxon rank sum), comparing Cases vs Controls; and characteristics of dosimetry group • Conditional logistic regression to examine Hgb-skin lesions while adjusting for co-variation (age, gender, smoking, betel-nut chewing, etc.). • For repeated measures, separate regressions (mixed models) with a random family effect.
Table 4. Summary statistics describing the physical and sociodemographic characteristics of the repeated measures (“dosimetry”) population (N=184).
Conclusions • Low hemoglobin may exacerbate the detrimental health effects of chronic arsenic poisoning. • While providing clean water remains the primary solution to the arsenic epidemic, improving nutrition and reducing iron deficiency may ameliorate the adverse health effects of arsenic.
We thank our colleagues, technicians, laboratory, and administrative staff at Dhaka Community Hospital and the Pabna Community Clinic in Bangladesh. We also acknowledge the academic assistance of Tom Smith and Paul Catalano, and the technical expertise of Janna Frelich, Thomas Can Geel, Ian James, Li Su, Ema Rodrigues and Meredith Jones. Acknowledgments
Grant Support • This publication was made possible by NIH grants T32 ES07069, research grants ES011622, ES05947, and center grant # ES00002. Its contents are solely the responsibility of the authors and do not represent the official views of the NIH.