PMID- 11425516
OWN - NLM
STAT- MEDLINE
DCOM- 20010816
LR  - 20190702
IS  - 0027-5107 (Print)
IS  - 0027-5107 (Linking)
VI  - 486
IP  - 2
DP  - 2001 Jul 12
TI  - Nucleotide excision repair gene expression in the rat conceptus during 
      organogenesis.
PG  - 113-23
AB  - DNA repair may be a determinant of the susceptibility of the conceptus to DNA 
      damaging teratogens. The nucleotide excision repair (NER) pathway repairs a 
      substantial amount of chemically induced DNA damage. The goals of this study were 
      to assess the coordinate expression of NER genes in the midorganogenesis-stage 
      rat conceptus and determine the consequences of exposure to the genotoxic 
      teratogen, 4-hydroperoxycyclophosphamide (4-OOHCPA), on NER gene expression. Most 
      NER genes were expressed at low levels in both yolk sac and embryo on gestational 
      day (GD) 10, with the exception of XPD, XPE and PCNA. No significant alterations 
      in gene expression occurred between GDs 10 and 11; in the yolk sac XPB expression 
      increased on GD12 compared to either GD10 or 11. In the embryo, XPE expression 
      increased between GDs 10 and 12, while hHR23B, XPB, ERCC1, and DNA polymerase 
      epsilon expression increased on GD12 relative to both GDs 10 and 11. Contrary to 
      gene expression data, XPB protein was found at high levels and XPD at low levels 
      in GDs 10-12 embryos and yolk sacs. Mirroring gene expression, high levels of 
      PCNA protein were found in both tissues; XPA protein levels were minimal in yolk 
      sac from GDs 10-12 but increased in the embryo from moderate on GD10 to high on 
      GD12. Therefore, NER gene expression during organogenesis was regulated in a 
      developmental stage- and tissue-specific manner. Exposure of the conceptus to a 
      teratogen, 4-OOHCPA, induced malformations without affecting NER transcript 
      levels. Thus, NER gene expression in the conceptus was unresponsive to regulation 
      by DNA alkylation.
FAU - Vinson, R K
AU  - Vinson RK
AD  - Department of Pharmacology & Therapeutics, McGill University, 3655 Promenade 
      Sir-William-Osler, Montreal, H3G-1Y6, Quebec, Canada.
FAU - Hales, B F
AU  - Hales BF
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Mutat Res
JT  - Mutation research
JID - 0400763
RN  - 0 (Teratogens)
RN  - 8N3DW7272P (Cyclophosphamide)
RN  - U880A4FUDA (perfosfamide)
SB  - IM
MH  - Animals
MH  - Cyclophosphamide/analogs & derivatives/*toxicity
MH  - DNA Repair/*genetics
MH  - Embryo, Mammalian/*physiology
MH  - Embryonic and Fetal Development/*drug effects
MH  - Gene Expression Regulation
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Teratogens/*toxicity
EDAT- 2001/06/27 10:00
MHDA- 2001/08/17 10:01
CRDT- 2001/06/27 10:00
PHST- 2001/06/27 10:00 [pubmed]
PHST- 2001/08/17 10:01 [medline]
PHST- 2001/06/27 10:00 [entrez]
AID - S0921877701000878 [pii]
AID - 10.1016/s0921-8777(01)00087-8 [doi]
PST - ppublish
SO  - Mutat Res. 2001 Jul 12;486(2):113-23. doi: 10.1016/s0921-8777(01)00087-8.