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A Trinidad

Publications and source records attributed to A Trinidad.

At least 37 records · Page 2Linked to original sources
PubMed1995

Alexithymia, affect recognition, and five factors of personality in substance abusers.

A total of 80 adults (40 normal volunteers, 40 substance abusers) participated in a study about alexithymia and five factors of personality, measured on the Toronto Alexithymia Scale and the NEO Five Factor Inventory, respectively, and their relationship to recognition of affect. The substance abusers scored the same as the age- and sex-matched normal volunteers on recognizing posed facial expressions, but higher on the alexithymia scale, while on Neuroticism and Extraversion they had lower scores on Agreeableness.

Adult↗
PubMed1994

Alexithymia, affect recognition, and the five-factor model of personality in normal subjects.

A total of 62 staff members from a general hospital participated in a study about alexithymia and the five-factor model of personality, measured by the Toronto Alexithymia Scale and the NEO Five Factor Inventory, respectively, and their relationship to recognition affect. Subjects with alexithymic characteristics were less able to recognize affective states in posed facial expressions and so may have modified their empathic capacity.

Adult↗
PubMed1991

Acetylator genotype-dependent expression of arylamine N-acetyltransferase in human colon cytosol from non-cancer and colorectal cancer patients.

Human epidemiological studies suggest an association between rapid acetylator phenotype and colorectal cancer. Acetylator genotype-dependent expression by the human colon of arylamine N-acetylation capacity, catalyzed by acetyl coenzyme A-dependent N-acetyltransferase(s) (EC 2.3.1.5) (NAT), may be an important risk factor in the initiation of colorectal cancer. Human colon cytosols from 48 fresh surgical samples were investigated for NAT activity toward p-aminobenzoic acid and the arylamine carcinogens 4-aminobiphenyl, 2-aminofluorene, and beta-naphthylamine. Apparent Vmax determinations of NAT activity toward these substrates indicated that 40 of these colons segregated into 3 distinct phenotypes. The distribution of the patients into rapid (5), intermediate (18), or slow (17) acetylators is a ratio that is not significantly different from the expected Hardy-Weinberg distribution of 3:16:21 (chi 2 = 2.206, P = 0.363). Significantly greater mean apparent Vmax levels were found in colons from rapid as compared to intermediate acetylators (1.5-3-fold) (P less than 0.001) and intermediate as compared to slow (2.5-3-fold) (P less than 0.005) acetylator phenotypes for the four arylamine substrates. Apparent Km determinations indicated that human colon NAT from rapid acetylators had a significantly lower affinity for the arylamine substrates (P less than 0.05) compared to intermediate or slow acetylator groups. No difference in apparent Km was detected for the cofactor acetyl coenzyme A between the three acetylator phenotypes. The colon samples were also tested for cytosolic N-hydroxy-2-acetylaminofluorene sulfotransferase activity and found to be monomorphically distributed for this enzyme activity. Of the 40 colon samples, 37 were from individuals of known pathology, 25 with colorectal cancer and 12 with no diagnosed neoplasia. Comparisons between mean apparent Vmax and mean apparent Km levels for each of the acetylator phenotypes indicated no significant differences between non-cancer and colorectal cancer patients. The distribution of rapid, intermediate, and slow acetylator phenotypes among the colon samples derived from colorectal cancer patients was precisely that predicted from published frequencies for the rapid and slow acetylator allele in Americans of African and European ancestry.

Acetylation↗
PubMed1990

Purification of hepatic polymorphic arylamine N-acetyltransferase from homozygous rapid acetylator inbred hamster: identity with polymorphic N-hydroxyarylamine-O-acetyltransferase.

The polymorphic acetyltransferase isozyme expressed in homozygous rapid acetylator inbred hamster liver cytosol was purified over 2000-fold by sequential Q-Sepharose fast-flow anion-exchange chromatography, Sephacryl S-200 high-resolution size-exclusion chromatography, Mono Q anion-exchange fast-protein liquid chromatography, and preparative polyacrylamide gel electrophoresis. The isozyme migrated as a single homogeneous monomer following both preparative and sodium dodecyl sulfate-polyacrylamide electrophoresis. The molecular weight was estimated at 34,170 following elution via size-exclusion chromatography and 35,467 following migration via sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The homogeneous polymorphic acetyltransferase exhibited a broad substrate specificity; it catalyzed the acetyl coenzyme A-dependent N-acetylation of p-aminobenzoic acid, carbocyclic arylamine carcinogens such as 2-aminofluorene, 4-aminobiphenyl and beta-naphthylamine, and heterocyclic arylamine carcinogens such as 2-aminodipyrido[1,2-a:3'2'd]imidazole and 3-amino-1-methyl-5H-pyrido[4,3-b]indole. It also readily catalyzed the acetyl coenzyme A-dependent metabolic activation (via O-acetylation) of N-hydroxy-2-aminofluorene to DNA adducts but not the metabolic activation (via intramolecular, N,O-acetyltransfer) of N-hydroxy-2-acetylaminofluorene or N-hydroxy-4-acetylaminobiphenyl to DNA adducts. Conversely, the partially purified monomorphic acetyltransferase isozyme from the same hamsters readily catalyzed the metabolic activation of N-hydroxy-2-acetylaminofluorene and N-hydroxy-4-acetylaminobiphenyl, and rates of metabolic activation of these substrates did not differ between homozygous rapid and slow acetylator liver, intestine, kidney, and lung cytosols. Heat inactivation rates for the purified polymorphic acetyltransferase isozyme were first order and indistinguishable for the acetyl coenzyme A-dependent N-acetylation and O-acetylation activities. The results strongly suggest the expression of a single polymorphic acetyltransferase product of the hamster polymorphic acetyltransferase gene that catalyzes both acetyl coenzyme A-dependent N-acetylation and O-acetylation of arylamine and N-hydroxyarylamine carcinogens but not the metabolic activation of N-hydroxy-N-acetylarylamines (arylhydroxamic acids) via intramolecular N,O-acetyltransfer. Consequently, acetylator genotype-dependent metabolic activation of N-hydroxyarylamines to a DNA adduct in hamster is catalyzed by direct O-acetylation of the hydroxyl group and not via sequential N-acetylation followed by N,O-acetyltransfer.

Acetyltransferases↗
PubMed1990

Relationship of Syrian inbred hamster acetylator genotype to the mutagenic activation of 2-aminofluorene.

The genetic constitution of mammalian enzymes involved in the metabolism of xenobiotics is one of the important factors responsible for large inter-individual differences in the rate of biotransformation and consequently the magnitude of genotoxic effects exerted in target tissues. The present study examines the mutagenic activation of 2-aminofluorene (AF) with hepatic post-mitochondrial (S9) preparations derived from homozygous rapid (Patr/Patr) acetylator and homozygous slow (Pats/Pats) acetylator Syrian inbred hamsters and its relationship to acetylator genotype. These hamster strains differ in their capacities for acetyl coenzyme A (AcCoA)-dependent, N-acetylation and O-acetylation of carcinogenic arylamines and their N-hydroxyarylamine metabolites. AF N-acetyltransferase activities determined in hepatic S9 fractions were 72.2 +/- 4.2 nmol/min/mg in rapid acetylator hamsters and 6.65 +/- 0.37 nmol/min/mg in slow acetylators, and were unaffected by the presence of 0.1 mM paraoxon. Mutagenic activation of AF was measured by reversion to histidine prototrophy in Salmonella typhimurium strain TA98. The metabolic activation of AF utilizing standard hepatic S9 preparations exhibited typical saturation kinetics that did not differ between acetylator genotypes. However, the addition of AcCoA to the standard S9 mix resulted in a dose-dependent reduction in the number of histidine revertants. In dose-response studies in which the concentrations of AF, AcCoA or S9 protein were varied, higher numbers of revertants were consistently generated with hepatic S9 derived from the slow acetylator compared to the rapid acetylator hamsters. These results indicate an acetylator genotype-dependent modulation of arylamine genotoxicity was reflected as a reduction in the levels of mutagenic metabolites generated in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetyl Coenzyme A↗
PubMed1989

Polymorphic expression of acetyl coenzyme A-dependent arylamine N-acetyltransferase and acetyl coenzyme A-dependent O-acetyltransferase-mediated activation of N-hydroxyarylamines by human bladder cytosol.

Human epidemiological studies suggest a genetic predisposition to bladder cancer among slow N-acetylators. The capacity of human bladder to N-acetylate arylamines, catalyzed by acetyl coenzyme A-dependent N-acetyltransferase(s) (EC 2.3.1.5) (NAT), may be an important step in the activation and/or deactivation of arylamines in the pathways leading to the initiation of bladder cancer. Another possible activation step is the direct O-acetylation of N-hydroxyarylamines via O-acetyltransferase(s) (OAT) to DNA-binding electrophiles. Human bladder cytosol from nine fresh autopsy specimens were investigated for NAT activity towards p-aminobenzoic acid, and the arylamine carcinogens 4-aminobiphenyl, 2-aminofluorene, and beta-naphthylamine. Apparent Km determinations indicated little difference in NAT affinity (100-300 microM) for any of the substrates between the nine individual bladders. However, the apparent Vmax determinations indicated that the bladders could be classified into rapid or slow acetylator phenotypes based on their NAT activity towards 4-aminobiphenyl, 2-aminofluorene, and beta-naphthylamine. Four of the bladder cytosols had mean activities significantly (P less than 0.01) higher (approximately 10-fold) than the mean NAT activities of the other five bladder cytosols towards each arylamine carcinogen. However, no significant difference was detected in their NAT activities using p-aminobenzoic acid as a substrate. The human bladder cytosols were also tested for their capacity to activate N-hydroxy-3,2'-dimethyl-4-aminobiphenyl to a DNA-binding electrophile through a direct OAT-mediated catalysis. The N-hydroxyarylamine OAT activity also discriminated between two levels of activation, being significantly (P = 0.0002) higher (about twofold) in the rapid N-acetylator bladder cytosols, that correlated (r = 0.94) with the measured levels of NAT activity in each bladder cytosol. These results suggest that NAT activity and OAT activity of the human bladder vary concordantly with N-acetylator phenotype. The polymorphic expression of these acetylation activities may be important risk factors in human susceptibility to bladder cancer from arylamine carcinogens.

2-Naphthylamine↗
PubMed1987

Acetylator genotype-dependent metabolic activation of carcinogenic N-hydroxyarylamines by S-acetyl coenzyme A-dependent enzymes of inbred hamster tissue cytosols: relationship to arylamine N-acetyltransferase.

A genetic polymorphism in S-acetyl coenzyme A (AcCoA)-dependent N-acetyltransferase has been associated with a differential risk for certain cancers in humans. In this study, several tissues from the inbred Syrian hamster with a genetically defined AcCoA-dependent N-acetyltransferase polymorphism (homozygous rapid acetylator, Bio. 87.20; homozygous slow acetylator, Bio. 82.73/H; and heterozygous acetylator, Bio. 87.20 X Bio. 82.73/H F1), were investigated for the relationship of arylamine N-acetyltransferase to the AcCoA-dependent metabolic activation of carcinogenic N-hydroxy (N-OH)-arylamines to bind to DNA (O-acetyltransferase). The levels of both 2-aminofluorene (AF) N-acetyltransferase and N-OH-AF O-acetyltransferase activity reflected the N-acetylator genotype in liver, intestine, kidney and lung cytosols. A significant acetylator gene--dose response for AF N-acetyltransferase and N-OH-AF O-acetyltransferase activities was observed in liver and lung cytosols. In contrast, acetylator genotype was not consistently expressed for the AcCoA-dependent N-acetylation of 4-aminobiphenyl (ABP), nor for the AcCoA-dependent metabolic activation of N-OH-ABP and N-OH-3,2'-dimethyl-4-aminobiphenyl in these same tissue cytosols. Two peaks of acetyltransferase activity were partially purified by ion exchange FPLC chromatography from the hepatic cytosol of both the homozygous rapid and homozygous slow acetylator hamster. In contrast to unfractionated cytosol, the isozyme(s) eluting first clearly demonstrated levels of AcCoA-dependent arylamine N-acetyltransferase and N-OH-arylamine O-acetyltransferase activities that were consistent with N-acetylator genotype (polymorphic) for all substrates tested. In contrast, the slower eluting isozyme(s) in each acetylator cytosol showed levels of AcCoA-dependent N- and O-acetyltransferase activities that did not vary with N-acetylator genotype (monomorphic). The AcCoA-dependent O-acetyltransferase activity of both the monomorphic and polymorphic peaks was paraoxon resistant. These studies demonstrate acetylator genotype-dependent control of AcCoA-dependent metabolic activation of N-OH-arylamines(O-acetylation) by polymorphic isozyme(s) similar to that for AcCoA-dependent N-acetylation of arylamines in the hamster. The polymorphic genetic control of N-OH-arylamine O-acetyltransferase may be an important risk factor for arylamine-induced cancer, in those species and tissues expressing appreciable levels of O-acetyltransferase activity.

Acetyl Coenzyme A↗
PubMed1987

Inheritance of acetylator genotype-dependent arylamine N-acetyltransferase in hamster bladder cytosol.

Acetyl coenzyme A-dependent arylamine N-acetyltransferase (EC 2.3.1.5) was examined in bladder cytosol derived from inbred Syrian hamsters. Expression of N-acetyltransferase activity towards p-aminobenzoic acid, p-aminosalicylic acid and 2-aminofluorene was acetylator genotype-dependent. Highest levels of bladder N-acetyltransferase activity were expressed in homozygous rapid acetylator hamsters (Bio. 87.20), lowest levels in homozygous slow acetylator hamsters (Bio. 82.73/H), and intermediate levels in Bio. 87.20 X Bio. 82.73/H F1 generation progeny. The N-acetyltransferase activity was acetylator genotype-dependent in both epithelial and non-epithelial bladder tissue. Genetic crosses using p-aminobenzoic acid and p-aminosalicylic acid as substrates indicated that bladder N-acetyltransferase activity is controlled via simple autosomal Mendelian inheritance of two codominant alleles at a single genetic locus. Acetylator genotype as assessed by bladder N-acetyltransferase activity was completely concordant with acetylator genotype as assessed by liver N-acetyltransferase activity. N-Acetyltransferase in slow acetylator bladder cytosol was both an apparent Km and Vmax variant compared to N-acetyltransferase in rapid acetylator bladder cytosol. These results suggest that genetic control of arylamine N-acetyltransferase in bladder urothelium may be a factor in hereditary predisposition to arylamine-induced bladder cancer.

Acetylation↗
PubMedDate not supplied

Inner ear malformations: Mondini's dysplasia.

Advances in imaging techniques are enabling the detection of increasing numbers of inner ear malformations. Mondini's dysplasia, whether alone or in association with other malformations, is one of those most frequently encountered. We report 4 cases of Mondini's dysplasia treated by us, discussing recent embryological and genetic findings.

Adolescent↗
PubMedDate not supplied

[Tympanosclerosis. I: proposed anatomical-surgical classification].

Tyrnpanosclerosis continues to be a clinically and pathogenically controversial topic. The options for dealing with it range from a conservative approach using hearing aids to surgery. With a view to justifying our therapeutic criteria, 29 cases of tympanosclerosis, out of a total of 200 surgical operations for otorrhea, were reviewed. An anatormical-surgical classification was established for use in approaching specific therapy for each particular case.

Cerebrospinal Fluid Otorrhea↗
PubMedDate not supplied

Acetylator genotype-dependent expression of arylamine N-acetyltransferase and N-hydroxyarylamine O-acetyltransferase in Syrian inbred hamster intestine and colon. Identity with the hepatic acetylation polymorphism.

Human epidemiological studies suggest an association between rapid acetylator phenotype and the incidence of colorectal cancer. Genetic regulation of acetyl coenzyme A-dependent N-acetyltransferase (NAT) and O-acetyltransferase (OAT) enzymatic activities may play a role in the metabolic activation of arylamine chemicals in the intestine and colon. In this study, the inheritance of acetyltransferase activity in the intestine and colon was investigated in the Syrian inbred hamster model. Relatively high levels of both arylamine NAT and N-hydroxyarylamine OAT activities were expressed in hamster intestine and colon cytosols, at levels similar to those in the liver. Acetylator genotype-dependent levels of NAT activity were expressed towards p-aminobenzoic acid and the carbocyclic arylamine carcinogens 2-aminofluorene (AF), 4-aminobiphenyl, and beta-naphthylamine. However, acetylator genotype-independent activity was found with the heterocyclic arylamine carcinogens 2-aminodipyrido[1,2-a:3',2'd]imidazole, 3-amino-1-methyl-5H-pyrido[4,3-b]indole, and 2-amino-9H-pyrido-[2,3,b]indole. F1 hybrid heterozygous acetylator progeny expressed unimodal levels of acetyltransferase activity intermediate between the homozygous rapid and slow acetylator parental strains. F2 generation progeny segregated into three modes (low, intermediate, and high) in a ratio of 1/2/1, and both sets of backcrosses yielded bimodal distributions of low and intermediate or high and intermediate in equal ratios. The genetic data is consistent with simple autosomal Mendelian inheritance of two codominant alleles (rapid and slow) at a single genetic locus, the polymorphic acetyltransferase gene. Levels of N-hydroxy-2-aminofluorene OAT activity were acetylator genotype-dependent in liver, intestine, and colon cytosols, which correlated well with AF NAT activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylation↗
PubMedDate not supplied

Identification and kinetic characterization of acetylator genotype-dependent and -independent arylamine carcinogen N-acetyltransferases in hamster bladder cytosol.

Recent studies from our laboratory have shown relatively high levels of polymorphic N-acetyltransferase (NAT)(EC 2.3.1.5) activity toward carcinogenic arylamines in urinary bladder cytosol of humans and in the inbred hamster model of the N-acetylation polymorphism. The expression of this polymorphism is of interest because of the higher incidence of bladder cancer among human slow acetylators with documented exposures to arylamine bladder carcinogens. In this study, arylamine NAT activity was partially purified and characterized in inbred hamster urinary bladder cytosols of defined acetylator genotype. Acetylator gene-dose response relationships were observed for the N-acetylation of p-aminobenzoic acid, p-aminosalicyclic acid, and the arylamine carcinogens 2-aminofluorene, 4-aminobiphenyl, and beta-naphthylamine in hamster bladder cytosol. Partial purification of hamster bladder cytosol by anion-exchange fast protein liquid chromatography yielded two NAT isozymes that catalyzed the N-acetylation of each of the arylamine substrates. The catalytic activity of the first isozyme was acetylator genotype-dependent (polymorphic), whereas the second isozyme appeared to be acetylator genotype-independent (monomorphic). Catalytic activities between homozygous rapid, heterozygous, and homozygous slow acetylator genotypes were compared with respect to both initial rates and apparent maximum velocities. Comparison of homozygous rapid and slow acetylator bladder cytosol showed that the apparent Vmax for 2-aminofluorene NAT activity was significantly higher in rapid than slow acetylators (6-fold in cytosol, 50-fold in the polymorphic NAT isozyme). These results suggest a key role for a polymorphic NAT isozyme, regulated by the acetylator genotype and expressed in urinary bladder cytosol, in the initiation of bladder cancer via arylamine carcinogens.

4-Aminobenzoic Acid↗
PubMedDate not supplied

Kinetic characterization of acetylator genotype-dependent and -independent N-acetyltransferase isozymes in homozygous rapid and slow acetylator inbred hamster liver cytosol.

Acetyl-coenzyme A (AcCoA)-dependent arylamine N-acetyltransferase (NAT) activity (EC 2.3.1.5) was examined in liver cytosol derived from homozygous rapid acetylator (Bio. 87.20) and homozygous slow acetylator (Bio. 82.73/H) Syrian inbred hamsters. Expression of NAT activity toward p-aminobenzoic acid (PABA), 2-aminofluorene (AF), and 4-aminobiphenyl (ABP) was acetylator genotype-dependent, whereas N-acetyltransferase activity toward isoniazid was acetylator genotype-independent. Two isozymes of NAT activity were partially purified by anion exchange fast protein liquid chromatography from the hepatic cytosol of both homozygous rapid and homozygous slow acetylator hamsters. The first eluting NAT isozyme exhibited a polymorphic expression toward AF, ABP, and PABA although the second eluting NAT isozyme exhibited a monomorphic expression across acetylator genotypes toward the same substrates. Determination of Michaelis-Menten kinetic constants in hepatic cytosol of homozygous rapid and slow acetylator hamsters suggests that PABA, AF, and ABP NAT activities were acetylator genotype-dependent because of catalysis by polymorphic NAT isozyme that is both an apparent Km and Vmax variant, whereas, the acetylator genotype-independent expression of isoniazid NAT activity appeared to result from catalysis via a common monomorphic NAT isozyme in both acetylator genotypes. Additional kinetic studies on the partially purified NAT isozymes of homozygous rapid and slow acetylator hamster liver confirmed that the polymorphic NAT isozyme exhibited a substantially higher apparent maximum velocity in homozygous rapid acetylators than slow acetylators toward PABA, AF, and ABP as well as acetylator genotype-related differences in the apparent Km toward each of these substrates. In contrast, the monomorphic NAT isozyme of both acetylator genotypes showed apparent Vmax levels of NAT activity that did not vary with acetylator genotype. Furthermore, the monomorphic NAT isozyme did not show acetylator genotype-related variations in apparent Km toward the arylamine carcinogens AF and ABP, although differences were noted for PABA and AcCoA. These results suggest that the acetylator genotype-dependent expression of AcCoA-dependent NAT activity in hamster hepatic cytosol toward arylamines is primarily accountable by structural variants (allozymes) of polymorphic NAT under the genetic regulation of the acetylator gene locus. The acetylator genotype-independent expression of isoniazid NAT activity is attributable to a common monomorphic NAT isozyme in both acetylator genotypes.

4-Aminobenzoic Acid↗
PubMedDate not supplied

The role of acetylator genotype on hepatic and extrahepatic acetylation, deacetylation, and sulfation of 2-aminofluorene, 2-acetylaminofluorene, and N-hydroxy-2-acetylaminofluorene in the inbred hamster.

In vitro rates of acetylation, deacetylation, and sulfation were measured with carcinogenic arylamine, arylamide, and arylhydroxamic acid substrates using enzyme preparations derived from inbred hamster tissues of known acetylator genotype. Homozygous rapid acetylators (Bio. 87.20), heterozygous acetylators (Bio. 87.20 X Bio. 82.72/H F1), and homozygous slow acetylators (Bio. 82.73/H) did not differ significantly with respect to paraoxon-resistant intermolecular N,N-transacetylation reactions from N-hydroxy-2-acetylaminofluorene to 4-aminoazobenzene in tissue cytosol. Similarly, they did not differ with respect to paraoxon-sensitive, microsomal N-hydroxy-2-acetylaminofluorene and 2-acetylaminofluorene deacetylase, and cytosolic N-hydroxy-2-acetylaminofluorene sulfotransferase activity. However, a gene dose-response relationship was observed in the same animals for cytosolic acetyl coenzyme A-dependent 2-aminofluorene N-acetyltransferase activity. Partial purification of liver cytosol yielded two paraoxon-resistant isozyme forms of acetyltransferase activity. The rates of one isozyme were acetylator genotype dependent (polymorphic), whereas the rates of the second isozyme appeared to be acetylator genotype independent (monomorphic). Acetyl coenzyme A-dependent 2-aminofluorene N-acetyltransferase activity was catalyzed at high rates by both isozymes, whereas transacetylation of 4-aminoazobenzene by various acyl donors (N-hydroxy-2-acetylaminofluorene, N-hydroxy-4-acetylaminobiphenyl, and acetyl coenzyme A) was catalyzed primarily (but not exclusively) by the monomorphic acetyltransferase isozyme. These results provide further information concerning the importance of acetylator genotype in the metabolism of carcinogenic arylamines and their metabolites.

2-Acetylaminofluorene↗
PubMedDate not supplied

Extrahepatic expression of N-acetylator genotype in the inbred hamster.

The genetic control of S-acetylcoenzyme A (AcCoA)-dependent N-acetyltransferase activity (EC 2.3.1.5) was investigated in liver, intestine, kidney, and lung cytosols derived from homozygous rapid acetylator (Bio. 87.20), heterozygous acetylator (Bio. 87.20 X 82.73/H F1), and homozygous slow acetylator (Bio. 82.73/H) Syrian inbred hamsters. AcCoA-dependent N-acetyltransferase activity was highest in hepatic cytosol, followed by intestine, kidney, and lung cytosol. In each of these tissues, cytosolic N-acetyltransferase exhibited an acetylator genotype-dependent activity with highest levels in homozygous rapid, intermediate levels in heterozygous F1 progeny, and lowest levels in homozygous slow acetylators. The ratio of N-acetyltransferase activity between acetylator genotypes was in general substrate dependent but not tissue dependent. Acetylator genotype-dependent N-acetyltransferase activity differences were highest for p-aminobenzoic acid, followed by p-aminosalicylic acid, 2-aminofluorene, and beta-naphthylamine. Expression of isoniazid N-acetyltransferase activity in each tissue was acetylator genotype independent. Determination of Michaelis-Menten kinetic constants in each tissue suggested that p-aminobenzoic acid N-acetyltransferase activity was acetylator genotype-dependent because of catalysis by an isozyme(s) that is both an apparent Km and a Vmax variant. In contrast, the acetylator genotype-independent expression of isoniazid N-acetyltransferase activity in each tissue appeared to result from a common isozyme(s) present in each tissue with equivalent kinetic constants in the two phenotypes. These data suggest that acetylator genotype-dependent expression of AcCoA-dependent N-acetyltransferase activity in extrahepatic tissues may play an important role in hereditary predisposition to toxicity and/or carcinogenesis in extrahepatic organs following exposure to arylamine drugs and foreign chemicals.

Acetylation↗