Aldehyde dehydrogenase isoenzymes in tumours - assay with possible prognostic value for oxazaphosphorine chemotherapy

• Autorzy: Wroczynski P. , Laskowska A. , Wierzchowski J. , Szubert A. , Polanski J. , Slowiaczek M.
• Języki publikacji: EN

Abstrakty

EN

A novel fluorimetric assay, allowing independent measurement of the activities of two principal cytosolic forms of human aldehyde dehydrogenase, ALDH-1 and ALDH-3 (known as a tumour-associated ALDH) was applied to estimate the activities of these isoenzymes in human liver and thyroid tumours. The assay is based on two artificial substrates, 6-methoxy-2-naphthaldehyde (MONAL-62) and 7-methoxy-1-naphthaldehyde (MONAL-71), 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 malignant and non-malignant tissue fragments, particularly in cancerous livers. Out of 16 tumours examined, only 4 exhibited ALDH-1 activities comparable to that found in the tumour-free tissue (0.5-2.5 U/g), while in the remaining 12 this activity was at least 10-fold lower. The ALDH-3 activity was detectable in about 40% of both tumour and tumour-free 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 (Km values for the fluorogenic naphthaldehydes as well as propanal inhibition profile) were similar to those of the purified ALDH-1. In 5 thyroid samples traces of ALDH-3 activity was detected, using MONAL-62 and NADP+ as substrates (maximum value 0.04 U/g). Possible prognostic value of the foregoing measurements for cyclophosphamide chemotherapy is discussed.

Słowa kluczowe

EN

aldehyde dehydrogenase; chemotherapy; oxazaphosphorine; fluorogenic substrate; cyclophosphamide; liver tumour; isoenzyme; thyroid tumour; tumour; naphthaldehyde

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 1998
• Tom: 45
• Numer: 1
• Opis fizyczny: p.33-40,fig.

Twórcy

autor

Wroczynski P.

• Medical Academy, S.Banacha 1, 02-097 Warsaw, Poland

autor

Laskowska A.

autor

Wierzchowski J.

autor

Szubert A.

autor

Polanski J.

autor

Slowiaczek M.

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