PubMed · 49083
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P Jacobs, D Dubovsky, H S King. 1975-04-12. Letter: Variety in general practice.. https://pubmed.ncbi.nlm.nih.gov/49083/
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A cyclophosphamide-resistant subline of a Yoshida ascites tumor was developed by giving increasing doses of the drug after transplantation. The effect of several alkylating agents on the cell proliferation of both the sensitive and resistance cell line was compared establishind dose response curves and D50 values. The developed subline revealed a 260 fold resistance to cyclophosphamide. It was completely cross-resistant to hydroperoxycyclophosphamide, whereas for triaziquone, N-oxide-mustard, and N-methyl-mustard only a partial cross resistance existed. These results give further evidence that cyclophosphamide and hydropeoxycyclophosphamide have the same mechanism of action. Regarding the other alkylating agents the results demonstrate differences concerning either the molecular mode of action or protecting effects. A decreased activation or uptake of substance is probably not the base for resistance.
Although carcinogens can be divided into various categories, i.e. viruses, physical agents and synthetic and naturally occurring chemicals, it is the latter that give rise to the greatest concern because of their number, quantity and distribution. Present methods of testing chemicals for potential carcinogenicity rely in the main on administration of these at maximally tolerated dose levels to animals, usually rodents, for the animals' lifetime. Such tests would be economically impractical for all chemicals to which man is exposed. New methods have recently been introduced to screen large numbers of chemicals quickly and cheaply which rely on the unifying hypothesis that all carcinogenic chemicals are electrophiles or must be converted to such by metabolism. These methods will be reviewed and compared with traditional methods of carcinogenicity testing, particularly as to their role in attempting to predict hazard to man.