Kinetics of arylamine N-acetyltransferase in tissues from human breast cancer.

Abstract

N-Acetyltransferase activity and Michaelis-Menten kinetic constants were determined in cancerous and non-cancerous breast tissues from 30 female patients with breast cancer. The results derived from tissue cytosol showed that 12 rapid, ten intermediate and eight slow acetylators based on p-aminobenzoic acid and 2-aminofluorene for substrates. The mean apparent Km values for the monomorphic substrate p-aminobenzoic acid and polymorphic substrate 2-aminofluorene were: 55.0 +/- 18.7, 114.0 +/- 30.0, and 137.0 +/- 37.2 microM; and 62.5 +/- 23.7, 166.0 +/- 67.0, and 239.0 +/- 76.6 microM for the slow, intermediate, and rapid enzymes, respectively. Compared to the enzymes from slow acetylators, the rapid acetylators exhibited mean apparent Vmax values eight- and ten-fold greater for p-aminobenzoic acid and 2-aminofluorene, respectively. A similar trend was obtained from the blood cytosols of cancerous patients and healthy volunteers. N-Acetyltransferase activity of breast cancerous and non-cancerous tissues were 1.5- and 2.2-fold different between rapid and slow acetylator with p-aminobenzoic acid and 2-aminofluorene as substrates, respectively. In breast cancerous tissues, 75% and 70% of the cytosolic N-acetyltransferase activity were inhibited under 2 mM of tamoxifen as substrates of 2-aminofluorene and p-aminobenzoic acid, respectively. Similar results were also found in non-cancerous tissues and blood samples from breast cancer patients and healthy volunteers. The effect of 1 mM tamoxifen on the N-acetyltransferase activity from breast cancerous tissues with positive estrogen receptor was 1.6-fold higher than that of negative estrogen receptor. This is the first demonstration to show that anti-estrogen drug can affect N-acetyltransferase activity in breast cancerous tissues. Therefore, this finding may provide a clue to the use of tamoxifen in prevention of human breast cancer.

• Authors: J H Lee, J G Chung, J M Lai, G N Levy, W W Weber
• Journal: Cancer letters (Cancer Lett) Vol. 111 Issue 1-2 Pg. 39-50 (Jan 01 1997) ISSN: 0304-3835 [Print] Ireland
• PMID: 9022126 (Publication Type: Journal Article)

Chemical References

• Anticarcinogenic Agents
• Carcinogens
• Fluorenes
• Neoplasm Proteins
• Tamoxifen
• 2-aminofluorene
• Arylamine N-Acetyltransferase
• 4-Aminobenzoic Acid

Topics

• 4-Aminobenzoic Acid (metabolism)
• Acetylation
• Anticarcinogenic Agents (pharmacology)
• Arylamine N-Acetyltransferase (metabolism)
• Breast (enzymology)
• Breast Neoplasms (enzymology)
• Carcinogens (metabolism)
• Female
• Fluorenes (metabolism)
• Humans
• Neoplasm Proteins (metabolism)
• Phenotype
• Tamoxifen (pharmacology)