title: Aflatoxin exposure is inversely associated with IGF1 and IGFBP3 levels in vitro and in Kenyan schoolchildren.
abstract: METHODS
  This study explores the relationship between aflatoxin and the insulin-like growth factor (IGF) axis and its potential effect on child growth.
  
  
  RESULTS
  One hundred and ninety-nine Kenyan schoolchildren were studied for aflatoxin-albumin adduct (AF-alb), IGF1 and IGF-binding protein-3 (IGFBP3) levels using ELISA. AF-alb was inversely associated with IGF1 and IGFBP3 (p < 0.05). Both IGF1 and IGFBP3 were significantly associated with child height and weight (p < 0.01). Children in the highest tertile of AF-alb exposure (>198.5 pg/mg) were shorter than children in the lowest tertile (<74.5 pg/mg), after adjusting for confounders (p = 0.043). Path analysis suggested that IGF1 levels explained ∼16% of the impact of aflatoxin exposure on child height (p = 0.052). To further investigate this putative mechanistic pathway, HHL-16 liver cells (where HHL-16 is human hepatocyte line 16 cells) were treated with aflatoxin B1 (0.5, 5 and 20 μg/mL for 24-48 h). IGF1 and IGFBP3 gene expression measured by quantitative PCR and protein in culture media showed a significant down-regulation of IGF genes and reduced IGF protein levels.
  
  
  CONCLUSIONS
  Aflatoxin treatment resulted in a significant decrease in IGF gene and protein expression in vitro. IGF protein levels were also lower in children with the highest levels of AFB-alb adducts. The data suggest that aflatoxin-induced changes in IGF protein levels could contribute to growth impairment where aflatoxin exposure is high.
authors.affiliation: Division of Epidemiology, School of Medicine, University of Leeds, Leeds, UK.
authors.forename: Jovita M
authors.initials: JM
authors.lastname: Castelino
authors.forename: Michael N
authors.initials: MN
authors.lastname: Routledge
authors.forename: Shona
authors.initials: S
authors.lastname: Wilson
authors.forename: David W
authors.initials: DW
authors.lastname: Dunne
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Mwatha
authors.forename: Kimani
authors.initials: K
authors.lastname: Gachuhi
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Wild
authors.forename: Yun Y
authors.initials: YY
authors.lastname: Gong
mesh_terms: D000293:Adolescent; D016604:Aflatoxin B1 / Q000633:toxicity; D000348:Aflatoxins / Q000097:blood / Q000633:toxicity*; D000418:Albumins; D001827:Body Height / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002460:Cell Line / Q000187:drug effects; D002648:Child; D003430:Cross-Sectional Studies; D005260:Female; D005506:Food Contamination / Q000032:analysis; D022781:Hepatocytes / Q000187:drug effects; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood* / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000032:analysis* / Q000235:genetics; D007630:Kenya; D008297:Male
chemical_list: D000348:Aflatoxins; D000418:Albumins; C583557:IGF1 protein, human; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; C098408:aflatoxin-albumin adduct; D007334:Insulin-Like Growth Factor I; D016604:Aflatoxin B1
keywords: Aflatoxins; Child growth; Exposure biomarker; IGFBP3; Insulin-like growth factor