DT-DIAPHORASE AND CYTOCHROME-B-5 REDUCTASE IN HUMAN LUNG AND BREAST-TUMORS

The level of expression of enzymes that can activate or detoxify biore ductive agents within tumours has emerged as an important feature in t he development of these anti-tumour compounds. The levels of two such reductase enzymes have been determined in 19 human non-small-cell lung tumours and 20 human breast tumours, together with the corresponding normal tissue. DT-diaphorase (DTD) enzyme levels (both expression and activity) were determined in these samples. Cytochrome b(5) reductase (Cytb(5)R) activity was also assessed. With the exception of six patie nts, the levels of DTD activity were below 45 nmol min(-1) mg(-1) in t he normal tissues assayed. DTD tumour activity was extremely variable, distinguishing two different groups of patients, one with DTD activit y above 79 nmol min(-1) mg(-1) and the other with levels that were in the same range as found for the normal tissues. In 53% of the lung tum our samples, DTD activity was increased with respect to the normal tis sue by a factor of 2.4-90.3 (range 79-965 nmol min(-1) mg(-1)). In 70% of the breast tumour samples, DTD activity was over 80 nmol min(-1) m g(-1) (range 83-267 nmol min(-1) mg(-1)). DTD expression measured by W estern blot correlated well with the enzyme activity measured in both tumour and normal tissues. The levels of the other reductase enzyme, C ytb(5)R, were not as variable as those for DTD, being in the same rang e in both tumour and normal tissue or slightly higher in the normal ti ssues. The heterogeneous nature of DTD activity and expression reinfor ces the need to measure enzyme levels in individual patients before th erapy with DTD-activated bioreductive drugs.