Induction of thymic lymphoma in mice administered the dideoxynucleoside ddC.
Groups of 10 male and 20 female B6C3F1 mice received 0, 500, or 1000 mg/kg/day 2'3'-dideoxycytidine (ddC) by gavage for 13 weeks. At the end of the 13-week exposure period all males and 10 females per group were necropsied while the remaining females were held for 1 month without further treatment. Thymic atrophy was present at the 13-week necropsy in male and female mice administered 1000 mg/kg/day and in females administered 500 mg/kg/day, but was not present in females following 1 month of recovery. Thymic lymphoma was present in 1 female that received 500 mg/kg/day and 1 female that received 1000 mg/kg/day. In a follow-up study groups of 70 female mice received 0, 500, or 1000 mg/kg/day for 13 weeks. At the end of the 13-week exposure period 20 mice per group were necropsied and the remaining animals held for 3 months without further treatment. Thymic atrophy was observed in ddC-exposed groups at the 13-week necropsy but not in mice allowed to recover for 13 weeks. Thymic lymphoma occurred in 3/50 mice that received 500 mg/kg/day and in 17/50 mice that received 1000 mg/kg/day but did not occur in mice from the vehicle control group.
Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.
V M
VM
Sanders
M R
MR
Elwell
J E
JE
Heath
B J
BJ
Collins
J K
JK
Dunnick
G N
GN
Rao
D
D
Prejean
C
C
Lindamood
R D
RD
Irwin
D000818:Animals; D000998:Antiviral Agents / Q000633:toxicity*; D001284:Atrophy / Q000139:chemically induced / Q000473:pathology; D001835:Body Weight / Q000187:drug effects; D005260:Female; D007441:Intubation, Gastrointestinal; D008223:Lymphoma / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009929:Organ Size / Q000187:drug effects; D013950:Thymus Gland / Q000473:pathology; D013953:Thymus Neoplasms / Q000139:chemically induced* / Q000473:pathology; D016047:Zalcitabine / Q000633:toxicity*
D000998:Antiviral Agents; D016047:Zalcitabine