Sensitivity of cell lines to mitomycin C.
OBJECTIVE
To determine the effect of pH on the cytotoxicity of mitomycin C on a wide range of established cell lines.


METHODS
Cultures of three human tumour cell lines, including two bladder carcinomas and one renal adenocarcinoma, and two mouse cell lines were treated with mitomycin C (concentration range 320 pM-50 microM) at a range of pH (5.8-7.8) for 2 h. The cytotoxicity of mitomycin C over this range was determined using a tetrazolium-dye-based microtitration assay.


RESULTS
The cytotoxicity of mitomycin C was significantly greater (confidence level > or = 95%) in acidic conditions (pH 5.8-6.0) than in neutral to alkaline pH (7.2-7.8) for three of the five cell lines. The same trend, although less marked, also occurred in the other two cell lines.


CONCLUSIONS
The cytotoxicity of mitomycin C was greater under acidic conditions for all these cell lines confirming that the activity of mitomycin C depends on pH and suggesting that the pH of the vehicle used for intravesical chemotherapy may be an important factor in the successful treatment of bladder carcinomas. The modification of pH by urine may explain some of the variation in success rates among patients treated intravesically with mitomycin C.
Watts
P L
PL
Bioengineering Unit, University of Strathclyde, Glasgow, UK.
Plumb
J A
JA
Courtney
J M
JM
Scott
R
R
D000230:Adenocarcinoma / Q000188:drug therapy; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D016685:Mitomycin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy
D000903:Antibiotics, Antineoplastic; D016685:Mitomycin