[Acquisition of resistance to anticancer agents by overproduction of target enzymes].
Antimetabolic anticancer agents possess their own target enzymes: that of methotrexate is dihydrofolate reductase; 5-fluorouracil and ZD1604, thymidylate synthase; hydroxyurea, ribonucleotide reductase; 2'-deoxycoformycin, adenosine deaminase; N-(phosphonacetyl)-L-aspartate, aspartate transcarbamylase. Overproduction of each target enzyme has been observed with various animal and human cell lines which acquired resistance to all these agents. These facts suggest that this is a common mechanism for resistance to these agents. Most of these resistant cells showed amplification of the corresponding genes in double minute chromosome or homogeneously stained region of the chromosome. The relation between the degree of resistance and those of enzyme overproduction, the expression and amplification of the gene coding for each enzyme protein in various resistant cell lines are demonstrated and discussed.
Inaba
M
M
Cancer Chemotherapy Center, Japanese Foundation for Cancer Research.
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004798:Enzymes / Q000235:genetics / Q000378:metabolism*; D005472:Fluorouracil / Q000494:pharmacology; D005784:Gene Amplification; D005815:Genetic Code; D006801:Humans; D008727:Methotrexate / Q000494:pharmacology; D009369:Neoplasms / Q000201:enzymology*
D000964:Antimetabolites, Antineoplastic; D004798:Enzymes; D005472:Fluorouracil; D008727:Methotrexate