Bladder cancer recurrence by implantation of exfoliated cells: is gamma-linolenic acid an effective tumoricidal agent?
OBJECTIVE
To compare the tumoricidal efficacy of meglumine gamma-linolenic acid (MeGLA), mitomycin C, epirubicin and water on two urothelial cell lines, and to establish the effect of serum protein levels derived from bladder cancer resection craters on the action of these agents.


METHODS
The human urothelial cell lines MGHU-1 and RT112 and their drug-resistant variants were exposed to short pulses of aqueous MeGLA, mitomycin, epirubicin and water. Both adherent and suspended cells were exposed to these agents. The MTT viable biomass assay and a clonogenic assay were used to establish tumoricidal efficacy. These experiments were then repeated to assess the effect of added serum proteins on the test results. Estimates of protein in the waste irrigation fluid from 10 patients undergoing transurethral resection of bladder tumour (TURBT) were used to select the quantity of protein used in the study, to establish the clinical relevance.


RESULTS
MeGLA caused > 95% reduction in the residual viable biomass of adherent cells, compared with < 50% reduction with any other agent. Both epirubicin and mitomycin were as effective as MeGLA in preventing colony formation from suspended drug-sensitive (parental) cells. However, using multidrug-resistant (MDR) cell lines, only MeGLA prevented any colony formation, although counts were greatly reduced by mitomycin and epirubicin. Water was least effective as a tumoricidal agent on both adherent and suspended cells. On the latter, water was markedly inactivated by adding 5% serum. TURBT waste irrigation fluid was found frequently to contain such quantities of serous fluid contamination, as shown by albumin estimates in waste fluid from 10 consecutive patients undergoing this procedure.


CONCLUSIONS
MeGLA is an effective tumoricidal agent against both parental and MDR cell lines. Its efficacy is maintained in the presence of clinically relevant serum contamination.
Department of Urology, Southampton University Hospitals NHS Trust, UK.
L Z
LZ
Solomon
A M
AM
Jennings
S J
SJ
Foley
B R
BR
Birch
A J
AJ
Cooper
D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D002295:Carcinoma, Transitional Cell / Q000517:prevention & control; D002448:Cell Adhesion; D019008:Drug Resistance, Neoplasm; D015251:Epirubicin / Q000494:pharmacology; D006801:Humans; D016685:Mitomycin / Q000494:pharmacology; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D009366:Neoplasm Seeding; D012709:Serum Albumin / Q000032:analysis; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014410:Tumor Stem Cell Assay; D001749:Urinary Bladder Neoplasms / Q000517:prevention & control; D014867:Water; D017965:gamma-Linolenic Acid / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D012709:Serum Albumin; D014867:Water; D015251:Epirubicin; D016685:Mitomycin; D017965:gamma-Linolenic Acid