PMID- 6484986
OWN - NLM
STAT- MEDLINE
DCOM- 19841114
LR  - 20190727
IS  - 0041-008X (Print)
IS  - 0041-008X (Linking)
VI  - 76
IP  - 1
DP  - 1984 Oct
TI  - Teratogenicity in vitro of two deacetylated metabolites of 
      N-hydroxy-2-acetylaminofluorene.
PG  - 161-71
AB  - In previous studies [E. Faustman-Watts, J. C. Greenaway, M. J. Namkung, A. G. 
      Fantel, and M. R. Juchau (1983) Teratology 27, 19-28] an embryo culture system 
      was utilized to investigate the role of biotransformation in the embryotoxicity 
      of 2-acetylaminofluorene. For this investigation, the capacity of two 
      deacetylated metabolites of N-hydroxy-2-acetylaminofluorene (N-OH-AAF) to produce 
      malformations in cultured whole rat embryos is reported. The relative capacities 
      of N-hydroxy-2-aminofluorene (N-OH-AF) and 2-nitrosofluorene (NF) to elicit 
      embryotoxic effects, including embryolethality, malformations, growth 
      retardation, and alterations in macromolecular content, were assessed and 
      compared with effects produced by N-OH-AAF and bioactivated 2-acetylaminofluorene 
      (AAF). Qualitatively similar patterns of malformations were produced by NF and 
      N-OH-AF. At initial concentrations greater than 60 microM, both deacetylated 
      compounds caused abnormalities in axial rotation (flexure), decreased viability, 
      and decreases in embryonic DNA and protein content. Both chemicals were active in 
      the absence of a bioactivating system. AAF produced a different spectrum of 
      defects, and was active only in the presence of a complete monooxygenase system. 
      The malformations produced by bioactivated AAF included abnormally open neural 
      tubes; flexure abnormalities were rarely observed. The primary defect elicited by 
      N-OH-AAF was prosencephalic hypoplasia. This chemical was active without an added 
      bioactivating system. Temporal studies demonstrated that exposure of embryos to 
      NF (128 microM) for as little as 2 hr was sufficient to elicit embryotoxic 
      effects. None of the individual metabolites appeared to be solely responsible for 
      the interruptions of neural tube closure produced by bioactivated AAF.
FAU - Faustman-Watts, E M
AU  - Faustman-Watts EM
FAU - Greenaway, J C
AU  - Greenaway JC
FAU - Namkung, M J
AU  - Namkung MJ
FAU - Fantel, A G
AU  - Fantel AG
FAU - Juchau, M R
AU  - Juchau MR
LA  - eng
GR  - HD-00836/HD/NICHD NIH HHS/United States
GR  - HD-04839/HD/NICHD NIH HHS/United States
GR  - HD-12717/HD/NICHD NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Fluorenes)
RN  - 0 (Nitroso Compounds)
RN  - 0 (Teratogens)
RN  - 34E9V9B29K (2-nitrosofluorene)
RN  - 53-95-2 (Hydroxyacetylaminofluorene)
RN  - 61M94X4V24 (N-hydroxy-2-aminofluorene)
RN  - 9M98QLJ2DL (2-Acetylaminofluorene)
SB  - IM
MH  - 2-Acetylaminofluorene/pharmacology
MH  - Abnormalities, Drug-Induced/etiology
MH  - Animals
MH  - Chromatography, High Pressure Liquid
MH  - Embryo, Mammalian/drug effects
MH  - Female
MH  - Fluorenes/*pharmacology
MH  - Hydroxyacetylaminofluorene/pharmacology
MH  - Nitroso Compounds/*pharmacology
MH  - Pregnancy
MH  - Rats
MH  - Rats, Inbred Strains
MH  - *Teratogens
EDAT- 1984/10/01 00:00
MHDA- 1984/10/01 00:01
CRDT- 1984/10/01 00:00
PHST- 1984/10/01 00:00 [pubmed]
PHST- 1984/10/01 00:01 [medline]
PHST- 1984/10/01 00:00 [entrez]
AID - 10.1016/0041-008x(84)90039-5 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 1984 Oct;76(1):161-71. doi: 10.1016/0041-008x(84)90039-5.