The implications of delta-aminolevulinic acid dehydratase (ALAD) polymorphism for lead kinetics and toxicity have been mainly studied in occupationally exposed adults. Therefore, our purpose was to ...evaluate the distribution of ALAD genotype and its association with biomarkers of exposure (PbB levels) and effect (Blood ZPP) among children living in a smelter community in Mexico. We recruited 569 children from nine elementary schools close to a smelter site. PbB was determined by electrothermal atomic absorption spectrometry. A polymerase chain reaction (PCR)-based protocol was used for ALAD genotyping. Zinc protoporphyrin (ZPP) in blood was measured by direct fluorometry. Most children (93.15%) were homozygous for ALAD 1−1, 6.67% were heterozygous for ALAD for 1−2, and one child was homozygous for ALAD 2−2. There was an increased proportion of ALAD 1−2/2−2 genotype with respect to PbB levels. The ZPP geometric mean was slightly higher in ALAD 1−1 genotype children (63.48 μ mol ZPP/mol Hb) than in those having the ALAD-2 genotype (58.22 μ mol ZPP/mol Hb; p = 0.051). Linear and quadratic models showed significant relationships between ZPP and PbB. A significant increase in the odds ratio (OR) for the effect of lead exposure on ZPP levels was observed for ALAD 1−1 children having PbB values above 20 μ g/dL, as compared to those having PbB levels below 10 μ g/dL (OR = 2.95, 95% CI = 1.45-5.97; p = 0.003), whereas no significant increases were observed for the ALAD 1−2/2−2 children. In summary, our results suggest that heme biosynthesis was less affected in ALAD 1−2/2−2 lead-exposed children than in those carrying the ALAD 1−1 genotype.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
During spermatogenesis, histones are replaced by protamines, which condense and protect sperm DNA. In humans, zinc contributes to sperm chromatin stability and binds to protamine P2 (HP2). Chemical ...interactions with nuclear protamines, which prevent normal sperm chromatin condensation, may induce changes in the sperm genome and thus affect fertility and offspring development. Since lead has a high affinity for zinc-containing proteins, we investigated lead interactions with HP2 as a novel mechanism of its toxicity to sperm. UV/vis and CD spectroscopy results indicated that HP2 binds Pb2+ at two different sites, causing a conformational change in the protein. They also provided evidence that thiol groups are primarily involved in Zn2+ and Pb2+ binding to HP2 and that HP2 may have additional binding sites for Pb2+ not related to Zn2+. HP2 affinities for Pb2+ and Zn2+ were very similar, suggesting that Pb2+ can compete with or replace Zn2+ in HP2 in vivo. This interaction of lead with HP2 resulted in a dose-dependent decrease in the extent of HP2−DNA binding, although lead interaction with DNA also contributed to this effect. Therefore, the ability of lead to decrease the level of HP2−DNA interaction may result in alterations to sperm chromatin condensation, and thus in reduced fertility.
Lead effects on protamine-DNA binding Quintanilla-Vega, Betzabet; Hoover, Dennis; Bal, Wojciech ...
American journal of industrial medicine,
September 2000, Letnik:
38, Številka:
3
Journal Article, Conference Proceeding
