PMID- 11754170
OWN - NLM
STAT- MEDLINE
DCOM- 20020225
LR  - 20151119
IS  - 0040-3709 (Print)
IS  - 0040-3709 (Linking)
VI  - 64
IP  - 6
DP  - 2001 Dec
TI  - Expression of base excision, mismatch, and recombination repair genes in the 
      organogenesis-stage rat conceptus and effects of exposure to a genotoxic 
      teratogen, 4-hydroperoxycyclophosphamide.
PG  - 283-91
AB  - BACKGROUND: DNA repair capability may influence the outcome of genotoxic 
      teratogen exposure. The goals of this study were to assess the expression of base 
      excision repair (BER), mismatch repair (MMR), and recombination repair (RCR) 
      genes in the mid-organogenesis rat conceptus and to determine the effects on 
      expression of exposure to the genotoxic teratogen, 4-hydroperoxycyclophosphamide 
      (4-OOHCPA). METHODS: The expression of 17 BER, MMR, and RCR genes was examined in 
      gestational day (GD) 10-12 rat conceptuses using the antisense RNA (aRNA) 
      technique. Embryos were cultured with 10 microM 4-OOHCPA to examine effects on 
      gene expression. RESULTS: Yolk sacs and embryos had similar gene expression 
      patterns for all three DNA repair pathways from GD10-12. Transcripts for APNG, 
      PMS1, and RAD54 were present at high concentrations in both tissues. The 
      remainder of the genes were expressed at low levels in yolk sac, with a few not 
      detected on GD10 and 11. In the embryo, transcripts for most genes were low on 
      GD10 and 11; several increased by GD12. After exposure to 4-OOHCPA for 24 hr, 
      XRCC1 and RAD57 expression decreased in yolk sac, whereas only RAD51 transcripts 
      decreased in the embryo. By 44 hr, transcripts for all BER genes decreased in 
      yolk sac; in the embryo, most BER, MMR, and RCR genes decreased, many below the 
      level of detection. CONCLUSIONS: The expression of DNA repair genes in the 
      mid-organogenesis rat conceptus is varied and subject to down-regulation by 
      4-OOHCPA. DNA repair gene expression may determine the consequences of 
      genotoxicant exposure during development.
CI  - Copyright 2001 Wiley-Liss, Inc.
FAU - Vinson, R K
AU  - Vinson RK
AD  - Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, 
      Canada, H3G 1Y6.
FAU - Hales, B F
AU  - Hales BF
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Teratology
JT  - Teratology
JID - 0153257
RN  - 0 (RNA, Antisense)
RN  - 0 (Teratogens)
RN  - 8N3DW7272P (Cyclophosphamide)
RN  - U880A4FUDA (perfosfamide)
SB  - IM
MH  - Alkylation
MH  - Animals
MH  - Base Pair Mismatch/*drug effects/genetics
MH  - *Cyclophosphamide/*analogs & derivatives
MH  - DNA Repair/*drug effects/genetics
MH  - Down-Regulation
MH  - Embryo, Mammalian/*drug effects/*metabolism
MH  - Nucleic Acid Hybridization
MH  - Organ Culture Techniques
MH  - RNA, Antisense/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Recombination, Genetic/*drug effects/genetics
MH  - *Teratogens
MH  - Time Factors
EDAT- 2001/12/26 10:00
MHDA- 2002/02/28 10:01
CRDT- 2001/12/26 10:00
PHST- 2001/12/26 10:00 [pubmed]
PHST- 2002/02/28 10:01 [medline]
PHST- 2001/12/26 10:00 [entrez]
AID - 10.1002/tera.1083 [pii]
AID - 10.1002/tera.1083 [doi]
PST - ppublish
SO  - Teratology. 2001 Dec;64(6):283-91. doi: 10.1002/tera.1083.