Genderspecific protective effect of hemoglobin on arsenicinduced skin lesions

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Gender-specific protective effect of hemoglobin
on arsenic-induced skin lesions

• David C. Christiani,MD,MPH,MS
• Dhaka, Bangladesh
• January 4, 2006

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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

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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.

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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.

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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.

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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.

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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.

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Methods

• Case-Control Study2001-2003, 900 case-control
  pairs (n1,800) recruited
• Physician-diagnosed lesions keratosis, spotted
  melanosis, Bowens 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

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Data collection and analysis

• Hgb determined by Sahlis 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.

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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.

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Table 4. Summary statistics describing the
physical and sociodemographic characteristics of
the repeated measures (dosimetry) population
(N184).
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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.

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Acknowledgments

• 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.

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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.