The involvement of apoptosis in etoposide-induced thymic atrophy.
A time- and dose-dependent thymic atrophy was observed in young male Fischer 344 rats dosed intraperitoneally with etoposide (10, 30, or 100 mg/kg). Histopathological examination of the thymus revealed that the pattern of cell death in the majority of thymocytes had a characteristic apoptotic morphology typified by nuclear condensation. This observation was supported by the formation of internucleosomal fragments of DNA in thymocytes isolated from animals dosed with etoposide. Administration of the protein synthesis inhibitor, cycloheximide (1.5 mg/kg, ip), 1 hr prior to etoposide inhibited the induction of apoptosis in thymocytes, assessed by both biochemical and histological criteria. Flow cytometric analysis of thymocytes from animals dosed with etoposide in vivo revealed the formation of both apoptotic cells and apoptotic bodies in contrast to previous in vitro studies which showed the formation of only apoptotic cells. Our data indicate that the induction of apoptosis in thymocytes is a major mechanism involved in etoposide-induced thymic atrophy.
Sun
X M
XM
Medical Research Council Toxicology Unit, University of Leicester, United Kingdom.
Carthew
P
P
Dinsdale
D
D
Snowden
R T
RT
Cohen
G M
GM
D000818:Animals; D017209:Apoptosis; D001284:Atrophy; D001835:Body Weight / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D004247:DNA / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004587:Electrophoresis, Agar Gel; D005047:Etoposide / Q000633:toxicity*; D005434:Flow Cytometry; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011863:Radioimmunoassay; D051381:Rats; D011916:Rats, Inbred F344; D013950:Thymus Gland / Q000187:drug effects* / Q000473:pathology; D013997:Time Factors
D005047:Etoposide; D004247:DNA; D003345:Corticosterone