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Genderspecific protective effect of hemoglobin on arsenicinduced skin lesions

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Title: Genderspecific protective effect of hemoglobin on arsenicinduced skin lesions


1
Gender-specific protective effect of hemoglobin
on arsenic-induced skin lesions
  • David C. Christiani,MD,MPH,MS
  • Dhaka, Bangladesh
  • January 4, 2006

2
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

3
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.

4
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.

5
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.

6
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.

7
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.

8
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

9
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.

10
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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19
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.

20
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.

21
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.
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