PMID- 10199582
OWN - NLM
STAT- MEDLINE
DCOM- 19990420
LR  - 20190819
IS  - 0300-483X (Print)
IS  - 0300-483X (Linking)
VI  - 132
IP  - 1
DP  - 1999 Jan 1
TI  - Persistent effect of in utero meso-2,3-dimercaptosuccinic acid (DMSA) on immune 
      function and lead-induced immunotoxicity.
PG  - 67-79
AB  - Meso-2,3-dimercaptosuccinic acid (DMSA) is a drug currently employed for cheltion 
      therapy in lead poisoning; however, little is known about its potential effects 
      on the immune system. To examine the effect of DMSA and its capacity to reverse 
      immunotoxicity resulting from exposure to lead in utero, female Fischer 344 rats 
      were administered lead acetate in drinking water from 2 weeks prior to mating 
      until parturition; DMSA was given by gavage on days 6-21 of gestation. The immune 
      function of the female offspring was tested at 13 weeks of age. The results 
      showed that lead (250 ppm) suppressed Th1-type responses (delayed-type 
      hypersensitivity (DTH), interferon gamma (IFN gamma) production), enhanced a 
      Th2-type response (interleukin-4 (IL-4) production), and increased tumor necrosis 
      factor alpha (TNF alpha) production from macrophages. DMSA treatment (60 mg/kg 
      per day) during pregnancy significantly lowered the blood lead levels of both the 
      embryos and the lactating dams as well as the milk lead level of lactating dams. 
      The chelation treatment also reversed the lead-induced alterations in pup body 
      weight, relative spleen weight, TNF alpha, and IL-4 production. But in utero 
      exposure to DMSA alone resulted in decreased DTH response in adult offspring. 
      This was likely due to a reduced cell recruitment, since plasma monocyte 
      chemoattractant protein-1 (MCP-1) levels were decreased. The DMSA-exposed 
      offspring also demonstrated increased interleukin-2 (IL-2) production. These 
      results suggest that DMSA reverses some of the lead-induced immunotoxicity; 
      however, this treatment itself during embryonic development produces subsequent 
      adult immunomodulation.
FAU - Chen, S
AU  - Chen S
AD  - Institute for Comparative and Environmental Toxicology, Department of 
      Microbiology and Immunology, College of Veterinary Medicine, Cornell University, 
      Ithaca, NY 14853-6401, USA.
FAU - Golemboski, K A
AU  - Golemboski KA
FAU - Sanders, F S
AU  - Sanders FS
FAU - Dietert, R R
AU  - Dietert RR
LA  - eng
GR  - ES05950/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 0 (Antidotes)
RN  - 0 (Chelating Agents)
RN  - 0 (Cytokines)
RN  - 2P299V784P (Lead)
RN  - DX1U2629QE (Succimer)
SB  - IM
MH  - Animals
MH  - Antidotes/*pharmacology
MH  - Cells, Cultured
MH  - Chelating Agents/*pharmacology
MH  - Cytokines/metabolism
MH  - Embryonic and Fetal Development/*drug effects/immunology
MH  - Female
MH  - Hypersensitivity, Delayed/immunology
MH  - Immune System/*drug effects
MH  - Lactation/metabolism
MH  - Lead/blood/*toxicity
MH  - Macrophages/drug effects/immunology
MH  - Male
MH  - Milk/metabolism
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects
MH  - Rats
MH  - Rats, Inbred F344
MH  - Spleen/immunology
MH  - Succimer/*pharmacology
EDAT- 1999/04/13 00:00
MHDA- 1999/04/13 00:01
CRDT- 1999/04/13 00:00
PHST- 1999/04/13 00:00 [pubmed]
PHST- 1999/04/13 00:01 [medline]
PHST- 1999/04/13 00:00 [entrez]
AID - S0300-483X(98)00139-5 [pii]
AID - 10.1016/s0300-483x(98)00139-5 [doi]
PST - ppublish
SO  - Toxicology. 1999 Jan 1;132(1):67-79. doi: 10.1016/s0300-483x(98)00139-5.