The uptake and metabolism of cyclophosphamide by the ovary.
The uptake of cyclophosphamide (CTX) and its metabolites was evaluated by injecting adult female rats with 14C-CTX on the morning of metestrous or proestrus. Rats were sacrificed 1 and 5 hours after 14C-CTX injection. The ovary, uterus, spleen, thymus, liver, kidney, anterior pituitary, duodenum, skeletal muscle and whole blood were isolated from each rat. Samples were combusted using a biological material oxidizer and the resulting CO2 was absorbed and counted. Liver and kidney had the highest uptake of 14C-radioactivity. The ovary appears to have 14C uptake comparable to the thymus and other tissues. Metabolism of CTX by the ovary was investigated by incubating 14C-CTX with human and rat granulosa cells and other ovarian cells obtained from pregnant mares' serum gonadotropin (PMSG)-primed immature rats, in separate experiments. The conversion of CTX to two marker metabolites, 4-ketocyclophosphamide and 4-hydroxycyclophosphamide was negligible and did not change in the presence of luteinizing hormone (LH). It is concluded that 1) following 14C-CTX injection, the ovary takes up a proportion of 14C-radioactivity comparable to other target tissues (e.g. thymus) and 2) the ovary is not capable of activating CTX in vitro in our system.
Ataya
K
K
Department of Ob/Gyn, MetroHealth Medical Center, Cleveland, OH.
Pydyn
E
E
Young
J
J
Struck
R
R
D000818:Animals; D003520:Cyclophosphamide / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D005260:Female; D006107:Granulosa Cells / Q000378:metabolism; D007986:Luteinizing Hormone / Q000502:physiology; D010053:Ovary / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D003520:Cyclophosphamide; D007986:Luteinizing Hormone