Minimal immunological changes in structurally malformed rats after prenatal exposure to cyclophosphamide.
In order to compare the sensitivities of morphological and immunological parameters in a teratology study, effects in day 20 rat fetuses were studied after a single exposure to the immunosuppressive cytostatic agent cyclophosphamide (CP) on either day 11 or day 15 of gestation. Teratological methods included evaluation of external and skeletal morphology. Furthermore histology, immunohistochemistry and flow cytometry were performed on fetal thymus, liver and spleen. Immune function was assayed using the Trichinella spiralis infection model. Treatment resulted in dose-dependent gross morphological malformations, and in addition in overt skeletal anomalies such as brachygnathia, wavy ribs, and lordosis. In contrast, the immunological parameters tested revealed only minimal differences between treated and control groups. These results suggest either a remarkable recovery of the immune system after treatment, or a relatively high resistance of the immune system to the present treatment.
Hessel
E M
EM
Unit Teratology, Endocrinology and Perinatal Screening, National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands.
Verhoef
A
A
van Loveren
H
H
Piersma
A H
AH
D000014:Abnormalities, Drug-Induced / Q000276:immunology*; D000818:Animals; D003520:Cyclophosphamide / Q000633:toxicity*; D005260:Female; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D007107:Immune System / Q000187:drug effects* / Q000196:embryology; D007124:Immunoenzyme Techniques; D007136:Immunoglobulins / Q000187:drug effects; D008208:Lymphatic System / Q000187:drug effects / Q000196:embryology; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011919:Rats, Inbred Strains; D017160:Trichinella spiralis / Q000276:immunology; D014235:Trichinellosis / Q000276:immunology
D007136:Immunoglobulins; D003520:Cyclophosphamide