PMID- 10463394
OWN - NLM
STAT- MEDLINE
DCOM- 19991026
LR  - 20190905
IS  - 0340-5761 (Print)
IS  - 0340-5761 (Linking)
VI  - 73
IP  - 4-5
DP  - 1999 Jun-Jul
TI  - Doxorubicin induces male germ cell apoptosis in rats.
PG  - 274-81
AB  - To clarify whether apoptosis is involved in doxorubicin (DXR)-induced testicular 
      toxicity and to identify the target germ cell type, adult Sprague-Dawley rats 
      were treated with a single intravenous dose of DXR (8 or 12 mg/kg) and euthanized 
      at 3, 6, 12, 24, and 48 h subsequently. Histologically, germ cell degeneration 
      was first found 6 h after dosing in meiotically dividing spermatocytes and early 
      round spermatids of seminiferous tubules at stage 1, and subsequently observed in 
      spermatogonia at stages I-VI showing ultrastructural characteristics of 
      apoptosis. Coincident with the appearance of morphological changes, degenerating 
      germ cells were shown to be undergoing apoptosis as revealed by in situ terminal 
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). The 
      frequency of TUNEL-labeled germ cells increased in a stage- and cell 
      type-specific manner, the peak of frequency gradually progressing from stage I of 
      seminiferous tubules to later stages with time after dosing, suggesting that the 
      damaged germ cells, especially spermatogonia, gradually underwent the processes 
      leading to apoptosis. DNA laddering on gel electrophoresis was apparent 24 and 48 
      h after dosing. The results demonstrate that apoptosis plays an important role in 
      the induction of testicular toxicity caused by DXR with meiotically dividing 
      spermatocytes and type A and intermediate spermatogonia as highly vulnerable 
      target cells.
FAU - Shinoda, K
AU  - Shinoda K
AD  - Pathology Unit, Hita Research Laboratories, Chemicals Inspection and Testing 
      Institute, Hita-shi, Oita, Japan. shinodak@hita.citi.or.jp
FAU - Mitsumori, K
AU  - Mitsumori K
FAU - Yasuhara, K
AU  - Yasuhara K
FAU - Uneyama, C
AU  - Uneyama C
FAU - Onodera, H
AU  - Onodera H
FAU - Hirose, M
AU  - Hirose M
FAU - Uehara, M
AU  - Uehara M
LA  - eng
PT  - Journal Article
PL  - Germany
TA  - Arch Toxicol
JT  - Archives of toxicology
JID - 0417615
RN  - 0 (Antineoplastic Agents)
RN  - 80168379AG (Doxorubicin)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*toxicity
MH  - Apoptosis
MH  - DNA/analysis
MH  - Doxorubicin/*toxicity
MH  - Electrophoresis, Agar Gel
MH  - Germ Cells/classification/*drug effects/*ultrastructure
MH  - In Situ Nick-End Labeling
MH  - Male
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Seminiferous Tubules/drug effects/pathology
MH  - Spermatogonia/drug effects
EDAT- 1999/08/27 00:00
MHDA- 1999/08/27 00:01
CRDT- 1999/08/27 00:00
PHST- 1999/08/27 00:00 [pubmed]
PHST- 1999/08/27 00:01 [medline]
PHST- 1999/08/27 00:00 [entrez]
AID - 10.1007/s002040050617 [doi]
PST - ppublish
SO  - Arch Toxicol. 1999 Jun-Jul;73(4-5):274-81. doi: 10.1007/s002040050617.