EVIDENCE OF IN-SITU ESTROGEN SYNTHESIS IN NITROSOMETHYLUREA-INDUCED RAT MAMMARY-TUMORS VIA THE ENZYME ESTRONE SULFATASE

A variety of indirect evidence suggests that mammary tumors can synthe size free estrogens in situ via the sulfatase enzyme. The present stud y utilized an isotopic kinetic technique to provide direct confirmatio n of local tumor synthesis. Animals bearing nitrosomethylurea (NMU)-in duced rat mammary tumors were infused with C-14-estrone as well as H-3 -estrone sulfate and plasma:tissue gradients for each steroid measured . Liver, serving as a control tissue, uniformly synthesized free estro ne from estrone sulfate with local synthesis in this organ providing a n average of 78 +/- 1.0% of the estrone in this tissue. In rat mammary tumors, five out of seven synthesized estrone locally with individual values ranging from 19 to 50% synthesized in tissue. These data indic ate that liver uniformly converts estrone sulfate to free estrone, whe reas the majority, but not all, breast tumors synthesize estrogen loca lly via this pathway. Copyright (C) 1996 Elsevier Science Ltd.