Effects on fetal thymocyte populations and postnatal T-cell-dependent immune functions after maternal exposure to 5-fluorouracil during pregnancy in mice.
5-Fluorouracil (5-FU) is a cytostatic anti-tumor drug which is known to have immunosuppressive activities. To assess the immunotoxic effects of 5-FU on fetal thymocyte populations and immune functions after birth, pregnant C57BL/6 mice were orally administered vehicle or 17 mg/kg/day of 5-FU during gestational days (GD) from 6 to 14. The fetal thymocyte populations were analyzed with flow cytometry (CD4/CD8 double staining), and immune functions (a mixed lymphocyte reaction, in vitro cytotoxic T-cell response, in vitro antibody-forming response) after birth were measured. Fetal thymus weight and thymocyte numbers were decreased by 5-FU administration. The decrease of the thymocytes was due mainly to the decrease of small CD4CD8 double positive (DP) thymocytes. The thymocyte numbers and populations recovered to the normal level 1 week after birth. The mixed lymphocyte response at the 6th week after birth tended to be slightly lower than the control levels, but the cytotoxic T-cell response and the antibody-forming response were the same as the control levels. These results suggest that immune functions might recover after birth, although maternal administration of 5-FU has a suppressive effect on fetal thymocyte maturation.
Inoue
Tomoaki
T
Department of Preclinical Science, Nippon Roche Research Center, 200 Kajiwara, Kamakura, Kanagawa 247-8530, Japan.
Horii
Ikuo
I
D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D005472:Fluorouracil / Q000008:administration & dosage / Q000633:toxicity*; D007107:Immune System / Q000187:drug effects* / Q000276:immunology; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D038081:Organogenesis / Q000187:drug effects* / Q000276:immunology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D013950:Thymus Gland / Q000187:drug effects* / Q000196:embryology / Q000276:immunology / Q000473:pathology
D007166:Immunosuppressive Agents; D005472:Fluorouracil