PMID- 10817665
OWN - NLM
STAT- MEDLINE
DCOM- 20000802
LR  - 20190905
IS  - 0340-5761 (Print)
IS  - 0340-5761 (Linking)
VI  - 74
IP  - 1
DP  - 2000 Mar
TI  - Induction and inhibition of testicular germ cell apoptosis by fluoroacetate in 
      rats.
PG  - 33-9
AB  - Fluoroacetate (FA), an inhibitor of aconitase, is known to lower the 
      intracellular level of adenosine triphosphate (ATP), which recently has been 
      suggested to be a possible determinant of the form of cell death, apoptosis or 
      necrosis. To investigate which form of germ cell death occurs in FA-induced 
      testicular toxicity, adult Sprague Dawley rats were given a single oral dose of 
      FA (0.5 or 1.0 mg/kg) and euthanized at 3, 6, 12, 24, 48, and 72 h thereafter. 
      Germ cell degeneration was histologically first found in early round spermatids 
      at stage I and in spermatogonia at stages II-IV of seminiferous tubules 6 and 12 
      h, respectively, after dosing. Degenerating spermatogonia exhibited 
      characteristic features of apoptosis as demonstrated by both electron microscopy 
      and in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling 
      (TUNEL), whereas spermatids did not. At the 24 and 48 h time points, degenerating 
      spermatids were continually present and subsequently formed multinucleated giant 
      cells, while the number of degenerating spermatogonia and TUNEL-labeled 
      spermatogonia was drastically and/or significantly decreased compared to those 
      from the control group, indicating that spontaneous male germ cell apoptosis is 
      inhibited. Coincident with these morphological changes, DNA laddering on gel 
      electrophoresis was apparent only 12 h after dosing. The results demonstrate that 
      FA induces either apoptosis or necrosis of male germ cells in the early stage 
      after dosing and subsequently inhibits spontaneous apoptosis.
FAU - Shinoda, K
AU  - Shinoda K
AD  - Pathology Unit, Hita Laboratories, Chemicals Evaluation and Research Institute, 
      Hita-shi, Oita, Japan. shinoda-kazutoshi@hita.cerij.or.jp
FAU - Mitsumori, K
AU  - Mitsumori K
FAU - Uneyama, C
AU  - Uneyama C
FAU - Uehara, M
AU  - Uehara M
LA  - eng
PT  - Journal Article
PL  - Germany
TA  - Arch Toxicol
JT  - Archives of toxicology
JID - 0417615
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Fluoroacetates)
RN  - 9007-49-2 (DNA)
RN  - EC 4.2.1.3 (Aconitate Hydratase)
SB  - IM
MH  - Aconitate Hydratase/*antagonists & inhibitors
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - DNA/chemistry/isolation & purification
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Energy Metabolism/drug effects
MH  - Enzyme Inhibitors/*pharmacology
MH  - Fluoroacetates/*pharmacology
MH  - Germ Cells/*drug effects/ultrastructure
MH  - In Situ Nick-End Labeling
MH  - Male
MH  - Microscopy, Electron
MH  - Necrosis
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Seminiferous Tubules/cytology/drug effects/ultrastructure
MH  - Spermatids/drug effects/ultrastructure
MH  - Testis/*cytology/drug effects/pathology
EDAT- 2000/05/19 09:00
MHDA- 2000/08/06 11:00
CRDT- 2000/05/19 09:00
PHST- 2000/05/19 09:00 [pubmed]
PHST- 2000/08/06 11:00 [medline]
PHST- 2000/05/19 09:00 [entrez]
AID - 10.1007/s002040050649 [doi]
PST - ppublish
SO  - Arch Toxicol. 2000 Mar;74(1):33-9. doi: 10.1007/s002040050649.