Actions of immunosuppressor drugs on the development of an experimental ovarian tumor.
Immunosuppression has been related to the incidence of tumor apparition, including endocrine tumors. The intrasplenic ovarian tumor (luteoma) is a typical benign endocrine tumor that develops under high gonadotropin stimulation and, from the immunological perspective, is located in a critical organ involved in immune response. To establish if immunosuppression could alter the development of this experimental tumor, the effects of cyclosporin A (CsA) and dexamethasone (Dex) were evaluated. After surgery, tumor-bearing and sham animals were kept without treatment for 4 weeks; thereafter, they were distributed into CsA (25 mg/kg), Dex (0.1 mg/kg), or vehicle (75:25 castor oil:ethanol) groups and were injected on alternate days for 50 days. Body weight was evaluated weekly. Animals were sacrificed after a jugular vein blood sample was obtained. Thymi were weighed. Tumors were measured and placed in formaline for histological studies. Serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL), and estradiol were measured by radioimmunoassay. Hematological parameters were determined. CsA induced a significant decrease in survival rates both in tumor-bearing and sham animals (P < 0.01). Dex significantly impaired weight increase in both groups of animals. CsA induced a significant weight loss in sham animals, not observed in tumor-bearing animals. Dex induced thymus weight loss in both groups, whereas CsA induced thymus weight loss only in sham animals. Only Dex induced a decrease in lymphocyte number in both groups. CsA induced an increase in monocyte number only in sham animals. Treatments did not alter LH, FSH, or estradiol, whereas PRL was increased by CsA only in sham rats. Neither Dex nor CsA induced any significant variations in tumor volume, nor did they alter tumor histology. In addition, no visible metastases or alterations in other organs were observed. We conclude that, though immunological parameters were altered by the treatments, immunosuppressor drugs did not condition tumor development. In addition, tumors secrete one or more factor/s that counteract CsA effect.
Instituto de Biología y Medicina Experimental-Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad de Buenos Aires, Vuelta de Obligado 2490, (1428) Buenos Aires, Argentina.
E
E
Sorianello
R
R
Schillaci
A
A
Chamson-Reig
V
V
Lux-Lantos
C
C
Libertun
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000097:blood; D018311:Luteoma / Q000378:metabolism / Q000473:pathology*; D009368:Neoplasm Transplantation; D009929:Organ Size / Q000187:drug effects; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D010052:Ovariectomy; D010053:Ovary / Q000637:transplantation; D011388:Prolactin / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000473:pathology*; D013950:Thymus Gland / Q000473:pathology; D016042:Transplantation, Heterotopic
D007166:Immunosuppressive Agents; D004958:Estradiol; D003907:Dexamethasone; D016572:Cyclosporine; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone