Induction of Thymic Lymphoma in Mice Administered the Dideoxynucleoside ddC

Abstract

Induction of Thymic Lymphoma in Mice Administered the Dideoxynucleoside ddC. Sanders, V. M., Elwell, M. R., Heath, J. E., Collins, B, J., Dunnick, J. K., Rao, G. N., Prejean, D., Lindamood, C., III, and Irwin, R. D. (1995). Fundam. Appl. Toxicol. 27, 263-269. 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 3150 mice that received 500 mg/kg/day and in 17150 mice that received 1000 mg/kg/day but did not occur in mice from the vehicle control group.