PMID- 12606156
OWN - NLM
STAT- MEDLINE
DCOM- 20030509
LR  - 20190826
IS  - 0009-2797 (Print)
IS  - 0009-2797 (Linking)
VI  - 145
IP  - 1
DP  - 2003 Mar 6
TI  - Prenatal expression of N-acetyltransferases in C57Bl/6 mice.
PG  - 77-87
AB  - Exposure to carcinogens such as 4-aminobiphenyl (4ABP), found in tobacco smoke 
      and other combustion products, results in the formation of detectable levels of 
      4ABP-hemoglobin adducts in cord blood and 4ABP-DNA adducts in conceptal tissue. 
      The presence of these adducts requires that the parent compound undergo 
      biotransformation. When exposure occurs in utero, the maternal, placental and 
      conceptal tissues are all possible sites for the formation of DNA-reactive 
      products. One step in the activation of 4ABP is catalyzed by N-acetyltransferases 
      (NAT). The expression of NAT was evaluated in gestational day (GD) 10-18 
      conceptal tissues from C57Bl/6 mice. There was a quantitative increase in NAT1 
      and NAT2 mRNAs with increasing gestational age that was also reflected in 
      age-related changes in functional protein measured as 4ABP-NAT activity. The 
      ability to acetylate 4ABP increased from GD10 to 18 and was lower in conceptal 
      tissue than in adult liver. The potential toxicologic significance of prenatal 
      NAT expression was assessed by formation of 4ABP-DNA adducts. At GD 15 and 18, 
      4ABP-DNA adducts were detected by immunohistochemistry 24 h following a single 
      oral dose of 120 mg 4ABP/kg. Based on nuclear fluorescence, conceptual 4ABP-DNA 
      adducts were present at similar levels at GD15 and 18. Levels of 4ABP-DNA adducts 
      were significantly higher in maternal liver compared with the conceptus. Results 
      from this study show that both NAT genes were expressed prenatally and that 
      functional enzymes were present. These data support the possible in situ 
      generation of reactive products by the conceptus. The relative contributions of 
      maternal activation of 4ABP and that by the conceptus remain to be determined.
FAU - McQueen, Charlene A
AU  - McQueen CA
AD  - Department of Pharmacology and Toxicology, College of Pharmacy, The University of 
      Arizona, PO Box 210207, Tucson, AZ 85721, USA. mcqueen@pharmacy.arizona.edu
FAU - Mitchell, M Kimberly
AU  - Mitchell MK
FAU - Dang, Lanvi N
AU  - Dang LN
FAU - Chau, Binh
AU  - Chau B
FAU - Tjalkens, Ronald B
AU  - Tjalkens RB
FAU - Philbert, Martin A
AU  - Philbert MA
LA  - eng
GR  - ES06694/ES/NIEHS NIH HHS/United States
GR  - ES08846/ES/NIEHS NIH HHS/United States
GR  - ES09812/ES/NIEHS NIH HHS/United States
GR  - ES10047/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Ireland
TA  - Chem Biol Interact
JT  - Chemico-biological interactions
JID - 0227276
RN  - 0 (Aminobiphenyl Compounds)
RN  - 0 (Carcinogens)
RN  - 0 (DNA Primers)
RN  - 0 (Isoenzymes)
RN  - 0 (RNA, Messenger)
RN  - 16054949HJ (4-biphenylamine)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A1)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A2)
RN  - EC 2.3.1.5 (Arylamine N-Acetyltransferase)
RN  - EC 2.3.1.5 (N-acetyltransferase 1)
SB  - IM
MH  - Aminobiphenyl Compounds/toxicity
MH  - Animals
MH  - Arylamine N-Acetyltransferase/*genetics
MH  - Base Sequence
MH  - Carcinogens/toxicity
MH  - Cytochrome P-450 CYP1A1/metabolism
MH  - Cytochrome P-450 CYP1A2/metabolism
MH  - DNA Primers
MH  - Female
MH  - Isoenzymes/*genetics
MH  - Liver/embryology/enzymology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Pregnancy
MH  - RNA, Messenger/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
EDAT- 2003/02/28 04:00
MHDA- 2003/05/13 05:00
CRDT- 2003/02/28 04:00
PHST- 2003/02/28 04:00 [pubmed]
PHST- 2003/05/13 05:00 [medline]
PHST- 2003/02/28 04:00 [entrez]
AID - S0009279702002405 [pii]
AID - 10.1016/s0009-2797(02)00240-5 [doi]
PST - ppublish
SO  - Chem Biol Interact. 2003 Mar 6;145(1):77-87. doi: 10.1016/s0009-2797(02)00240-5.