De novo expression of transfected human class 1 aldehyde dehydrogenase (ALDH) causes resistance to oxazaphosphorine anti-cancer alkylating agents in hamster V79 cell lines. Elevated class 1 ALDH activity is closely correlated with reduction in DNA interstrand cross-linking and lethality.

Human class 1 aldehyde dehydrogenase (hALDH-1) can oxidize aldophosphamide, a key aldehyde intermediate in the activation pathway of cyclophosphamide and other oxazaphosphorine (OAP) anti-cancer alkylating agents. Overexpression of class 1 ALDH (ALDH-1) has been observed in cells selected for survival in the presence of OAPs. We used transfection to induce de novo expression of human ALDH-1 in V79/SD1 Chinese hamster cells to clearly quantitate the role of hALDH-1 expression in OAP resistance.

Oxazaphosphorine-specific resistance in human MCF-7 breast carcinoma cell lines expressing transfected rat class 3 aldehyde dehydrogenase.

Overexpression of either class 1 or class 3 aldehyde dehydrogenase (ALDH) has been found in cell lines selected for resistance to the oxazaphosphorine (OAP) alkylating anticancer agent cyclophosphamide (CPA). Direct oxidation of the CPA metabolic intermediate aldophosphamide (ALDO) is catalyzed efficiently in vitro by the class 1 ALDH isozyme, but the involvement of the class 3 isozyme in OAP resistance is problematic since in vitro studies do not show efficient oxidation of ALDO. Cell lines were established that express stably transfected rat class 3 ALDH to model the potential role of this isozyme in OAP resistance.

Protection by transfected glutathione S-transferase isozymes against carcinogen-induced alkylation of cellular macromolecules in human MCF-7 cells.

Increased expression of glutathione S-transferase (GST) isozymes has been correlated with development of resistance both to cytotoxic anticancer agents and to genotoxic carcinogens. While most anticancer agents are poor GST substrates, the model alkylating carcinogen 4-nitroquinoline-1-oxide (NQO) is a good substrate for human pi class GST (hGSTP1-1) and murine GST mu-1 (mGSTM1-1), but not human GST alpha-2 (hGSTA2-2). We investigated whether expression of these GST isozymes in stably transfected clonal cell lines could protect against the genotoxic and cytotoxic effects of NQO.