Cancer zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Letters, zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA ll(l981) 323-339 o Elsevier/ North-Holland Scientific Publishers Ltd. 323 zyxwvut AMINOGUANIDINE REVERSAL OF THE INHIBITORY EFFECTS OF ORNITHINE ANALOGS ON THE IN VITRO CLONOGENIC SURVIVAL OF THE R3327AT PROSTATE-DERIVED TUMOR* WARREN D.W. HESTON,** DAVID W. LAZAN and WILLIAM R. FAIR The Division of Urology, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110 (U.S.A.) (Received 23 July 1980) (Revised version 3 September1930) (Accepted 20 October 1980) SUMMARY In in vivo studies with the Copenhagen rat prostrate-derived tumor cell lines, the activity of omithine decarboxylase (ODC) of these lines were as sensitive to inhibition by cr-difluoromethylomithine (wDFM0) as normal prostatic tissue. The in vitro growth of the tumor in calf serum was inhibited by ODC inhibitors ar-methylomithine and a-difluoromethylomithine. This inhibition was partially reversed by the diamine oxidase inhibitor amino- guanidine. Further, (r-DFMO was not inhibitory to the growth of these cells in sera which lacked diamine oxidase activity, but was inhibitory when diamine oxidase was added. INTRODUCTION The activity of the enzyme ornithine decarboxylase (ODC) has been positively correlated with growth process in a large number of normal and malignant tissues [ 11,171. ODC is the rate limiting step in the formation of the diamine putrescine from ornithine; putrescine being required for the further synthesis of the polyamines spermidine and spermine. The ability of a cell to form polyamines is thought to be necessary for RNA and DNA synthesis. It has been shown that ODC enzymes from various different tissues exhibit different properties [3,4,13]. Furthermore, in vivo adminis- tration of the suicide substrate oldifluoromethylornithine (a-DFMO) *Supported in part by Public Health Service Grant CA23665 from the National Cancer Institutes of Health, of the Department of Health, Education and Welfare. **To whom reprint requests should be addressed.