ALDEHYDE DEHYDROGENASE ISOENZYMES IN TUMORS - ASSAY WITH POSSIBLE PROGNOSTIC VALUE FOR OXAZAPHOSPHORINE CHEMOTHERAPY

A novel fluorimetric assay, allowing independent measurement of the ac tivities of two principal cytosolic forms of human aldehyde dehydrogen ase, ALDH-1 and ALDH-3 (known as a tumour-associated ALDH) was applied to estimate the activities of these isoenzymes in human liver and thy roid tumours. The assay is based on two artificial substrates, 6-metho xy-2-naphthaldehyde (MONAL-62) and 7-methoxy-1-naphthaldehyde (MONAL-7 1), exhibiting excellent substrate properties toward various forms of human ALDH (see Wierzchowski et al., 1997, Anal. Biochem, 245, 69-78). We have found significant differences in ALDH activities between mali gnant and non-malignant tissue fragments, particularly in cancerous li vers. Out of 16 tumours examined, only 4 exhibited ALDH-1 activities c omparable to that found in the tumour-free tissue (0.5-2.5 U/g), while in the remaining 12 this activity was at least l0-fold lower. The ALD H-3 activity was detectable in about 40% of both tumour and tumour-fre e liver samples (maximum value 1.5 U/g). Comparison of 13 pathological thyroid fragments revealed ALDH activities in the range of 0.02 to 0. 35 U/g, with two malignant samples showing activities of 0.27 and 0.18 U/g. Both substrate specificity and kinetic behaviour of the thyroid ALDH (K-m values for the fluorogenic naphthaldehydes as well as propan al inhibition profile) were similar to those of the purified ALDH-1. I n 5 thyroid samples traces of ALDH-3 activity was detected, using MONA L-62 and NADP(+) as substrates (maximum value 0.04 U/g). Possible prog nostic value of the foregoing measurements for cyclophosphamide chemot herapy is discussed.