KINETICS OF ARYLAMINE N-ACETYLTRANSFERASE IN TISSUES FROM HUMAN BREAST-CANCER

N-Acetyltransferase activity and Michaelis-Menten kinetic constants we re determined in cancerous and non-cancerous breast tissues from 30 fe male patients with breast cancer. The results derived from tissue cyto sol showed that 12 rapid, ten intermediate and eight slow acetylators based on p-aminobenzoic acid and 2-aminofluorene for substrates. The m ean apparent K-m values for the monomorphic substrate p-aminobenzoic a cid and polymorphic substrate 2-aminofluorene were: 55.0 +/- 18.7; 114 .0 +/- 30.0, and 137.0 +/- 37.2 mu M; and 62.5 +/- 23.7, 166.0 +/- 67. 0, and 239.0 +/- 76.6 mu M for the slow, intermediate, and rapid enzym es, respectively. Compared to the enzymes from slow acetylators, the r apid acetylators exhibited mean apparent V-max values eight- and ten-f old greater for p-aminobenzoic acid and 2-aminofluorene, respectively. A similar trend was obtained from the blood cytosols of cancerous pat ients and healthy volunteers. N-Acetyltransferase activity of breast c ancerous and non-cancerous tissues were 1.5- and 2.2-fold different be tween rapid and slow acetylator with p-aminobenzoic acid and 2-aminofl uorene as substrates, respectively. In breast cancerous tissues, 75% a nd 70% of the cytosolic N-acetyltransferase activity were inhibited un der 2 mM of tamoxifen as substrates of 2-aminofluorene and p-aminobenz oic acid, respectively. Similar results were also found in non-cancero us tissues and blood samples from breast cancer patients and healthy v olunteers. The effect of 1 mM tamoxifen on the N-acetyltransferase act ivity from breast cancerous tissues with positive estrogen receptor wa s 1.6-fold higher than that of negative estrogen receptor. This is the first demonstration to show that anti-estrogen drug can affect N-acet yltransferase activity in breast cancerous tissues. Therefore, this fi nding may provide a clue to the use of tamoxifen in prevention of huma n breast cancer. (C) 1997 Elsevier Science Ireland Ltd.