Abstract
The cytotoxicity of hexamethylmelamine (HMM) and its metabolites pentamethylmelamine (PMM), N,2,2,4,6-tetramethylmelamine (TMM) and hydroxymethylpentamethylmelamine (HMPMM) and of the alkylating agent triethylenemelamine (TEM) were studied on a cell line derived from a human ovarian cancer, by measuring [3H]TdR uptake. After 24 h of incubation all the tested compounds inhibited [3H]TdR uptake, but only at a concentration of 100 micrograms/ml. However, after 120 h incubation, concentrations of 0.1--10 micrograms/ml resulted in highly significant cytotoxicity. HMPMM and TEM were the most active and their effect was not reversed 72 h after their removal. In our in vitro system no metabolism of HMM was observed.
Highlights
Summary.-The cytotoxicity of hexamethylmelamine (HMM) and its metabolites pentamethylmelamine (PMM), N,2,2,4,6-tetramethylmelamine (TMM) and hydroxymethylpentamethylmelamine (HMPMM) and of the alkylating agent triethylenemelamine (TEM) were studied on a cell line derived from a human ovarian cancer, by measuring [3H]TdR uptake
HEXAMETHYLMELAMINE (HMM) is an anticancer drug which in Phase II trials has shown consistent activity in several human malignancies (Blum et al, 1973; Legha et al, 1976); its effectiveness has been demonstrated in ovarian cancer (Wilson et al, 1969) and oat-cell carcinoma of the lung (Takita & Didolkar, 1974)
The mechanism of action of HMM is unknown and, despite its structural similarity to triethylenemelamine (TEM) it does not appear to act as an alkylating agent (Worzalla et al, 1973)
Summary
Summary.-The cytotoxicity of hexamethylmelamine (HMM) and its metabolites pentamethylmelamine (PMM), N,2,2,4,6-tetramethylmelamine (TMM) and hydroxymethylpentamethylmelamine (HMPMM) and of the alkylating agent triethylenemelamine (TEM) were studied on a cell line derived from a human ovarian cancer, by measuring [3H]TdR uptake. The mechanism of action of HMM is unknown and, despite its structural similarity to triethylenemelamine (TEM) it does not appear to act as an alkylating agent (Worzalla et al, 1973). For this reason it can be used in combination therapy or in patients who have become resistant to these drugs (Johnson et al, 1978; Bonomi et al, 1979; Bolis et al, 1979). In the light of these considerations we decided to investigate the in vitro activity of HMM and its metabolites at different concentrations and times of exposure, Correspondence to: Mauirizio D)'Incalhi, M.D., Istituto di Ricercle Farmacologiche "Mario Negri", Via Eritrea, 62- -20157 Milain, Italy
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