Bis(4,7-dimethyl and 5-dinitro-1,10-phenanthroline) sulfato-oxovanadium(IV)-mediated in vivo male germ cell apoptosis

Oxovanadium(IV) [VO] complexes of 1,10-phenanthroline are a new class of po tent apoptosis-inducing cytotoxic agents against human testicular cancer ce lls in vitro. The present study investigated the in vivo ability of four(bi s)-chelated 1,10-phenanthroline [phen] complexes of sulfato-oxovanadium(IV) -VO(phen)(2), VO(Cl - phen)(2), VO(Me-2-phen)(2) and VO(NO2-phen)(2)-with a nd without substitutions, to induce testicular germ cell apoptosis. Male ge rm cell loss in mice was measured by determining the epididymal sperm count , testicular weight and histological evaluation of the testes. Repetitive i ntratesticular injection (7.5 mg kg(-1) testis(-1)) of bis-chelated 1,10-ph enanthroline complexes of oxovanadium(IV) with 4,7-dimethyl [VO(Me-2-phen)( 2)] and 5-dinitro [VO(NO2-phen)(2)] substitution led to decreased sperm cou nts and reduced testicular weights. Histopathological examination of testic ular sections from VO(Me2-phen)(2)-and VO(NO2-phen)(2)-treated mice reveale d a marked inhibition of spermatogenesis and preferential loss of maturing, as well as elongated spermatids. In situ evaluation of seminiferous tubule cross-sections by terminal deoxynucleotidyl transferase-mediated FITC-deox yuridine triphosphate nick end-labeling (TUNEL) and laser scanning confocal microscopy showed characteristic apoptotic germ cells delineating the peri phery of the seminiferous tubules. The ability of bis-chelated 4,7-dimethyl - and 5-dinitro-substituted 1,10-phenanthroline complexes of oxovanadium(IV ) to induce germ cell apoptosis in vivo may have potential utility in the t reatment of human testicular germ cell tumors. Copyright (C) 2001 John Wile y & Sons, Ltd.