title: A new approach for evaluating in vivo anti-leukemic activity using the SCE assay. An application on three newly synthesised anti-tumour steroidal esters.
abstract: Three newly synthesised steroidal esteric derivatives of nitrogen mustard (compounds 1-3) were comparatively studied on a molar basis regarding their ability to induce sister chromatid exchanges (SCEs) in normal human lymphocytes in vitro and therapeutic effects on leukemia P388 bearing mice. Compounds 1 and 3 are modified steroidal esters of p-methyl-m-N,N-bis(2-chloroethyl)amino benzoic acid, and compound 2 is a modified steroidal ester of chlorambucil. All compounds induced statistically significant increases in SCEs and decreases in proliferation rate indices (PRIs) of cultured human lymphocytes and significantly increased the life span of P388 bearing mice. In this study, the doses applied for therapeutic purposes upon leukemia P388 bearing mice in vivo were derived from cytogenetic observations in normal human lymphocytes in vitro. A substantially better therapeutic effect was obtained compared to the effect achieved after the use of quite higher doses related with LD(10) values. We have demonstrated that the order of anti-tumour effectiveness of the treatment schedules of the three newly synthesised compounds tested (at doses derived from cytogenetic observations) coincides with the order of the cytogenetic effects they induce. The SCE assay appears to have an application in the clinical prediction of tumour sensitivity to potential chemotherapeutics.
authors.affiliation: Laboratory of Biology and Genetics, Medical School, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
authors.forename: Venetia
authors.initials: V
authors.lastname: Karayianni
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Mioglou
authors.forename: Zafiroula
authors.initials: Z
authors.lastname: Iakovidou
authors.forename: Dionysios
authors.initials: D
authors.lastname: Mourelatos
authors.forename: Manolis
authors.initials: M
authors.lastname: Fousteris
authors.forename: Anna
authors.initials: A
authors.lastname: Koutsourea
authors.forename: Evaggelia
authors.initials: E
authors.lastname: Arsenou
authors.forename: Sotiris
authors.initials: S
authors.lastname: Nikolaropoulos
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007941:Leukemia P388 / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009588:Nitrogen Mustard Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D013256:Steroids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D018906:Antineoplastic Agents, Alkylating; D009588:Nitrogen Mustard Compounds; D013256:Steroids