In vivo studies of cadmium-induced apoptosis in testicular tissue of the rat and its modulation by a chelating agent.
In vivo CdCl2-induced apoptotic DNA fragmentation in the testes of the male Wistar rat has been demonstrated on agarose gel. Characteristic DNA migration patterns (laddering) provide evidence of apoptosis (programmed cell death) in testicular tissue of rats administered CdCl2 at a level of 0.03 mmol/kg 48 h previously. Evidence that administration of an appropriate cadmium chelating agent within the first 24 h can suppress some or all of the apoptotic changes in testicular DNA has also been obtained for the first time. A greater reduction in apoptosis is observed as the interval between the administration of the cadmium and that of the chelating agent is shortened. Administration of monoisoamyl meso-2,3-dimercaptosuccinate (Mi-ADMS) to male Wistar rats given CdCl2 is effective in the modulation of the typically apoptotic DNA fragmentation and associated histopathologic injury when the antagonist is given within approximately 1 h after the CdCl2 exposure. When the antagonist is given at later times there is a progressively more pronounced degradation of the DNA into oligonucleotides as seen in the typical electrophoretic DNA ladder pattern found with apoptosis. There is also a progressive increase in histopathological tissue changes as the antagonist is administered at progressively greater intervals after the cadmium.
Xu
C
C
Department of Chemistry, Vanderbilt University, Nashville, TN 37235, USA.
Johnson
J E
JE
Singh
P K
PK
Jones
M M
MM
Yan
H
H
Carter
C E
CE
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001485:Basement Membrane / Q000187:drug effects; D002104:Cadmium / Q000008:administration & dosage / Q000633:toxicity*; D019256:Cadmium Chloride; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D002614:Chelating Agents / Q000494:pharmacology*; D002712:Chlorides / Q000008:administration & dosage / Q000633:toxicity*; D002843:Chromatin / Q000473:pathology; D004249:DNA Damage; D004587:Electrophoresis, Agar Gel; D007274:Injections, Intraperitoneal; D007985:Leydig Cells / Q000166:cytology / Q000187:drug effects; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012708:Sertoli Cells / Q000166:cytology / Q000187:drug effects; D013094:Spermatozoa / Q000166:cytology / Q000187:drug effects; D004113:Succimer / Q000494:pharmacology*; D013737:Testis / Q000166:cytology / Q000187:drug effects*
D002273:Carcinogens; D002614:Chelating Agents; D002712:Chlorides; D002843:Chromatin; D002104:Cadmium; D004113:Succimer; D019256:Cadmium Chloride