Aromatic amine acetyltransferase as a marker for colorectal cancer: environmental and demographic associations.

In this pilot, case-controlled investigation of 43 colorectal and 41 control male patients, we compared associations of colorectal cancer with the aromatic amine acetyltransferase polymorphism, nutritional and demographic characteristics, medical histories, industrial and occupational histories, and exposures from home environments and personal habits. Persons with the "fast" acetylator trait were at greater risk of colorectal cancer (odds ratio: 2.48; 95% confidence interval: 1.02, 6.03). Results that differed from previous reports were positive associations of colorectal cancer with agricultural and manufacturing industries and with consumption of meats prepared by smoking, curing, and barbecueing. As expected, exercise frequency, cruciferous vegetables, and dietary fiber served as protective factors.

Role of aromatic amine acetyltransferase in human colorectal cancer.

Hepatic arylamine acetyltransferase phenotype has been suggested to be an important risk factor for urinary bladder carcinogenesis in individuals with known exposure to aromatic amines. This study was performed to evaluate the relative distribution of fast- and slow-acetylator phenotypes both in a population of men, 45 to 75 years of age, with a history of colorectal cancer and in a matched control group. Acetyltransferase activity was determined by administration of sulfamethazine and by subsequent analysis of blood and urine samples for N-acetylsulfamethazine and sulfamethazine using high-pressure liquid chromatography. The control group was composed of 28 slow-, two intermediate-, and 11 fast-acetylator individuals, while the group of patients with a history of cancer consisted of 20 slow-, three intermediate-, and 20 fast-acetylator phenotypes. This higher relative proportion of fast acetylators in the patients with a cancer history was highly significant and is consistent with the hypothesis that aromatic amines could play a role in the etiology of human colorectal cancer.

Regulation of vertebrate liver HMG-CoA reductase via reversible modulation of its catalytic activity.

We have investigated the comparative biochemistry of in vitro regulation of HMG-CoA reductase (EC 1.1.1.34) in microsomal preparations from the livers of nine vertebrates. In all instances, reductase activity was rapidly and profoundly decreased by addition of MgATP. Reductase activities were restored to near or above initial levels after removal of MgATP and incubation with a crude, low molecular weight phosphatase preparation from rat liver cytosol. Restoration of reductase activity was inhibited both by NaF and by pyrophosphate, known inhibitors of phosphoprotein phosphatase activity. Liver cytosol of species other than the rat exhibits reductase phosphatase activity. The converter enzymes that catalyze modulation of MG-CoA reductase activity (reductase kinase and reductase phosphatase) thus appear to be ubiquitous in vertebrate liver. Interconversion in vitro of active and inactive forms of reductase probably is general for vertebrate liver also. The majority of the reductase present in vertebrate liver may be present in a catalytically inactive or latent form in vivo. Under the experimental conditions used, the fraction present in the active form is, for a given species, quite constant. Species to species, from 20-45% of the reductase appears to be present in the active form.