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PubMed1990

The inhibiting effect of PABA on photocarcinogenesis.

The efficacy of a 5% solution of para-aminobenzoic acid (PABA) to protect against photocarcinogenesis was tested in 6 groups, each of which contained 30 light pigmented hairless mice. The light source was a Phillips TL 40 W/12, which mainly emits UVB. PABA significantly retarded the tumor induction time (p less than 0.05) and reduced both tumor yield and carcinoma yield (p less than 0.05). The dorsal skin of the mice was removed and weighed. The mean weight of UVR-exposed mice skin protected with PABA did not differ from that of the controls, but in the non-protected UVR-exposed mice the skin samples were significantly heavier (p less than 0.05).

4-Aminobenzoic Acid↗
PubMed1991

Nutritional factors and antimicrobials on development of infective larvae of subperiodic Brugia malayi (Nematoda: Filarioidea) in Anopheles quadrimaculatus and Aedes aegypti (Diptera: Culicidae).

The effects of nutritional factors and antimicrobials on the development of infective larvae of subperiodic Brugia malayi in susceptible Anopheles quadrimaculatus Say and Aedes aegypti (L.) were investigated. Larvae of both species of mosquitoes were reared on brewers yeast or a 1:1 brewers yeast-liver powder mixture. After emergence, one-half of the adults from each rearing condition were maintained on a 10% sucrose solution and the other half on a 10% sucrose solution containing 0.1% p-aminobenzoic acid (PABA). Females of both species of mosquitoes that fed on B. malayi-infected jirds showed a significant increase in the ineffective rate and intensity of infectiveness when the mosquito larvae were reared on the brewers yeast-liver powder diet. The addition of 0.1% PABA to the adult diet increased numbers of infective larvae of B. malayi that developed in Ae. aegypti but not in An. quadrimaculatus. The intensity of infectiveness of B. malayi was significantly greater when An. quadrimaculatus females were provided with a second blood meal from an uninfected jird and when females of both species were maintained on different concentrations of an antimicrobial solution.

4-Aminobenzoic Acid↗
PubMed1986

Sodium and potassium intakes in a representative population sample: estimation from 24 h urine collections known to be complete in a Cambridgeshire village.

1. A representative sample of eighty men aged 25-44 years from a Cambridgeshire village, each carried out one 24-h urine collection which was analysed for sodium, potassium, creatinine and urea content. The completeness of the collections was verified using oral doses of p-aminobenzoic acid (PABA; the PABA check test). 2. In the seventy-one collections shown to be complete, the average 24 h excretion of Na was 172 mmol and the average 24 h excretion of K was 74 mmol. 3. Fifty-one of these men's wives also made complete 24 h collections. The average content of these was 128 mmol Na and 61 mmol K. 4. Self reports and creatinine index would have identified as incomplete only 29 and 14% respectively of collections so judged by PABA. 5. Average excretion of 150 mmol Na/d was similar to estimated intakes of 140-167 mmol/d from the National Food Survey (Bull & Buss, 1980).

4-Aminobenzoic Acid↗
PubMedDate not supplied

Effects of vitamin C on arylamine N-acetyltransferase activity in human liver tumor cells.

Arylamine N-acetyltransferase (NAT) activity in a human liver tumor (heptoma) cell line was inhibited by vitamin C. Using high performance liquid chromatography, NAT activity on the acetylation of 2-aminofluorene and p-aminobenzoic acid was examined. Two assay systems were performed, one with cellular cytosols, the other with intact liver tumor cell suspensions. The NAT activity in a human liver tumor cell line was inhibited by vitamin C in a dose-dependent manner in both types of examined system: i.e. the greater the concentration of vitamin C in the reaction, the greater the inhibition of NAT activities in both systems examined. The data also indicated that vitamin C decreased the apparent Km and Vmax of NAT enzymes from human liver tumor cells in both systems examined. This report is the first demonstration which showed vitamin C effect on human liver tumor cell NAT activity.

4-Aminobenzoic Acid↗
PubMed1997

Sheep tissue acetyl coenzyme A-dependent arylamine N-acetyltransferases.

Acetyl coenzyme A-dependent arylamine N-acetyltransferases (NATs), EC 2.3.1.5. were measured in sheep tissues (N = 14) using p-aminobenzoic acid (PABA) as a substrate. Specific activities of liver, kidney, and lung NATs were 5.3 x 10(-3) +/- 1.4 (mean +/- SE) nmoles.min-1.mg protein-1, 3.4 x 10(-3) +/- 1.1 nmoles.min-1.mg protein-1, 2.5 x 10(-3) +/- 1.2 nmoles.min-1.mg protein-1, respectively. Km values were 53 +/- 3 microM for liver, 34 +/- 2 microM for kidney, and 28 +/- 2 microM for lung tissue. Optimum pH for the acetylation reaction was found as 7.5. The enzyme activity was stable for at least 6 months in all tissues, when stored at -70 degrees C. The enzyme from sheep tissues were quite heat-stable. Inhibition studies showed that N-ethylmaleimide was a potent inhibitor of sheep tissue NAT enzymes.

4-Aminobenzoic Acid↗
PubMed1995

Pteroylpolyglutamate synthesis by lung- and culture-derived Pneumocystis carinii.

Pneumocystis carinii synthesizes folates de novo from exogenous p-aminobenzoic acid (pABA). Lung-derived organisms take up [3H]pABA in vitro except in the presence of sulfamethoxazole. Supernatants from spinner-flask cultures take up [3H]pABA if they were inoculated with lungs from infected rats, but not if they were inoculated with lungs from uninfected rats. P. carinii folates consist primarily of pteroylpentaglutamates. Plasmodium falciparum, in contrast, contains primarily pteroyltetraglutamates. Culture-derived organisms synthesize folates at a four-fold higher specific activity than lung-derived organisms, possibly because they contain less contaminating lung debris. These data suggest that P. carinii remains metabolically active in culture for at least 4 days.

4-Aminobenzoic Acid↗
PubMed1977

Folate metabolism in malaria.

It is known that malaria parasites are inhibited by sulfonamides and antifolate compounds, require 4-aminobenzoic acid for growth, and respond only partly to intact folic and folinic acids. Biochemical data obtained during the last decade on the synthesis of nucleic acid precursors and on folate enzymes in malaria support the hypothesis that malaria parasites are similar to microorganisms that synthesize folate cofactors de novo. Sulfa drugs inhibit plasmodial dihydropteroate synthase (EC 2.5.1.15). Pyrimethamine and many other antifolate compounds bind to tetrahydrofolate dehydrogenase (EC 1.5.1.3) of the parasite more tightly than to the host enzyme. However, the metabolic consequences of the depletion of folate cofactors as a result of drug inhibition are not yet known. Other areas to be studied are the origin of the pteridine moiety of folates, the addition of glutamate(s) in folate cofactor biosynthesis, the means by which intact, exogenous folates affect malarial growth, and demonstration of the enzymes and reactions involving N(5)-methyl tetrahydrofolate.

4-Aminobenzoic Acid↗
PubMed1999

The PABA story.

The qualities of para-aminobenzoic acid (PABA) are discussed and an account is given of how it came to be the favourite sunscreen of the post World War II era. Slowly, however, dermatologists became aware that it was a fairly common sensitizer and that it tended to cross-sensitize with compounds of similar chemical structure both in contact with the skin and given as systemic drugs. Furthermore, continued exposure to chemicals of this type could lead to autoimmune responses especially systemic lupus erythematosus and dermatomyositis. Discussion of these complications from the use of PABA took place at two meetings of the Dermatological Association of Australia in 1964 and 1965, and played a part in the slow withdrawal of PABA from sunscreens.

4-Aminobenzoic Acid↗
PubMed1982

Perinatal development of N-acetyltransferase in hepatic and extrahepatic tissues of guinea pigs.

Hepatic and extrahepatic distribution and the perinatal developmental pattern of p-aminobenzoic acid (PABA)-N-acetyltransferase (E.C.2.3.1.5) in guinea pig liver, lung, and placenta were studied. In adult guinea pigs, kidney and small intestine enzyme specific activities were equivalent to hepatic activity. Lung enzyme activity was about 15% of that in adult liver. No sex differences in hepatic or extrahepatic distribution of enzyme levels were evident. The perinatal development study revealed that fetal as well as neonatal animals are capable of N-acetylation. The peak in liver and lung activity occur between 3 and 8 days after birth. Placenta has about 50% of adult liver activity for PABA-N-acetylation and it declines near term. These data indicate that extrahepatic organs of guinea pigs significantly contribute to PABA-N-acetylation.

4-Aminobenzoic Acid↗
PubMed1986

Acetyltransferase in humans: development and tissue distribution.

Acetyltransferase with p-aminobenzoic acid (PABA) as substrate was investigated in the cytosolic fraction of the placenta, liver, adrenals, lungs, kidneys, intestine from human fetuses and the liver, lungs, kidneys and intestinal mucosa from adult subjects. All tissue specimens assayed catalyzed the acetylation of PABA at a significant rate. The activity (expressed as nmol of product formed/min/mg protein; mean +/- SE) was 1.10 +/- 0.59 in the fetal liver, 0.66 +/- 0.04 in the placental and 3.87 +/- 0.53 in the adult liver cytosol. Among the fetal tissues, the adrenals had the highest (2.36 +/- 0.78) and the gut the lowest activity (0.71 +/- 0.11). The acetyltransferase activity (mean +/- SE) in the lungs, kidneys and intestinal mucosa from adult subjects was 1.19 +/- 0.15; 1.34 +/- 0.04 and 3.80 +/- 0.34, respectively.

4-Aminobenzoic Acid↗
PubMed1995

Evidence for the lack of hepatic N-acetyltransferase in suncus (Suncus murinus).

The abilities of liver cytosol fractions from the suncus and Sprague-Dawley (SD) rats to N-acetylate aniline, p-aminobenzoic acid, p-aminosalicylic acid and 2-aminofluorene (AF) were compared. The cytosol from rats N-acetylated these substrates at efficient rates, whereas the cytosol from the suncus did not N-acetylate these substrates at detectable rates. When AF was given to the suncus, 2-acetylaminofluorene (AAF), a metabolite of AF formed by N-acetyltransferase (NAT), was not detectable in serum, whereas the metabolite was seen clearly in rats. Northern blot and Southern blot analyses, using cDNAs coding for human NATs as probes, indicated that not only the transcripts but also the genes of the enzymes were undetectable in suncus. These results suggest that the suncus is among the few species known to lack NATs.

2-Acetylaminofluorene↗
PubMed1978

[Porphyria cutanea tarda: possible treatment and its results (author's transl)].

In 4 of 12 patients with porphyria cutanea tarda (PCT) treatment with p-aminobenzoic acid (PABA) achieved normal porphyrin excretion and disappearance of the skin changes. But this result is far worse than that obtained with the venesection method of Ippen. PABA treatment should, therefore, be discontinued.--Among 56 patients (37 males, 19 females) given chloroquine treatment (twice 125 mg per week), normal porphyrin excretion and disappearance of the skin changes occurred in 32 after an average duration of treatment of 8 months, while in 21 (15 males and 6 females) an improvement set in after an average treatment duration of only 5 months so far. The treatment failed in three patients, but one of them lapsed his treatment and one died of an intercurrent disease, so that only one can be reckoned a true failure of chloroquine treatment.

4-Aminobenzoic Acid↗
PubMed2003

Neonatal ontogeny of murine arylamine N-acetyltransferases: implications for arylamine genotoxicity.

Age-related changes in the expression of xenobiotic biotransformation enzymes can result in differences in the rates of chemical activation and detoxification, affecting responses to the therapeutic and/or toxic effects of chemicals. Despite recognition that children and adults may exhibit differences in susceptibility to chemicals, information about when in development specific biotransformation enzymes are expressed is incomplete. N-acetyltransferases (NATs) are phase II enzymes that catalyze the acetylation of arylamine and hydrazine carcinogens and therapeutic drugs. The postnatal expression of NAT1 and NAT2 was investigated in C57Bl/6 mice. Hepatic NAT1 and NAT2 messenger RNAs (mRNAs) increased with age from neonatal day (ND) 4 to adult in a nonlinear fashion. The presence of functional proteins was confirmed by measuring NAT activities with the isoform selective substrates p-aminobenzoic acid and isoniazid, as well as the carcinogens 2-aminofluorene and 4-aminobiphenyl (4ABP). Neonatal liver was able to acetylate all of the substrates, with activities increasing with age. Protein expression of CYP1A2, another enzyme involved in the biotransformation of arylamines, showed a similar pattern. The genotoxicity of 4ABP was assessed by determining hepatic 4ABP-DNA adducts. There was an age-dependent increase in 4ABP-DNA adducts during the neonatal period. Thus, developmental increases in expression of NAT1 and NAT2 genes in neonates are associated with less 4ABP genotoxicity. The age-related pattern of expression of biotransformation enzymes in mice is consistent with human data for NATs and suggests that this may play a role in developmental differences in arylamine toxicity.

4-Aminobenzoic Acid↗
PubMed1992

Exocrine pancreatic insufficiency in presumed healthy elderly subjects.

A pilot study on exocrine pancreatic function, using the 2-day para-aminobenzoic acid (PABA) test, was performed on 21 healthy elderly and 26 healthy young subjects. A PABA excretion index (PEI) less than 55%, indicating moderate to severe exocrine pancreatic insufficiency (EPI), was found in 19% of the elderly group (95% confidence limits 5-42%). While the mean value of the PEI was significantly lower in the elderly compared with the young group (Mann-Whitney Z = 2.8, p less than 0.01), there was no significant difference when the elderly subgroup with PEI less than 55% was excluded. There was no evidence of a generalized moderate to severe decline in pancreatic exocrine function with increasing age; a mild to moderate decline cannot be excluded.

4-Aminobenzoic Acid↗
PubMed1990

Evaluation of tests of exocrine and endocrine pancreatic function in older patients with cystic fibrosis.

In order to determine the value of noninvasive tests in the analysis of pancreatic function in cystic fibrosis, 14 older cystic fibrosis patients were studied by a set of noninvasive tests of exocrine and endocrine pancreatic function. The tests, comprising trypsin, total amylase, pancreatic isoamylase, lipase, pancreatic polypeptide (PP), glucose and insulin in fasting serum, PP, glucose and insulin in postprandial serum, and p-aminobenzoic acid (PABA) excretion in urine, were compared to fecal fat excretion after discontinuation of pancreatic enzyme supplementation. Eleven of the 14 patients were found to have a fecal fat excretion of more than 7 g/day. Serum levels of trypsin, pancreatic isoamylase and lipase, and the urinary excretion of PABA showed significant negative correlations with fecal fat excretion. Endocrine pancreatic function was abnormal in the majority of patients with fibrocystic disease. Although serum trypsin, postprandial PP, and urinary PABA excretion were the most sensitive tests for severe exocrine pancreatic insufficiency, the differences in sensitivity were rather modest. Therefore, the type of test to be selected for clinical use is mainly dependent upon factors as accessibility, simplicity, patient's acceptability, and costs.

4-Aminobenzoic Acid↗
PubMed1995

Assessment of arylamine N-acetyltransferase (NAT1) activity in mononuclear leukocytes of cystic fibrosis patients.

The clearance of sulphamethoxazole (SMX), a compound metabolised primarily by the N-acetyltransferase NAT1, is increased in cystic fibrosis (CF) patients. We assessed the activity and kinetic properties of NAT1 in lysates of peripheral blood mononuclear leukocytes (MNL) from CF (n = 17) and control (n = 22) subjects using SMX and p-aminobenzoic acid (PABA) as test substrates. The Km and Vmax values of both substrates in MNL from CF patients and control subjects were not significantly different. The acetylation of PABA (100 microM) by intact MNL from CF patients (n = 4) was not different from the observed in intact MNL from controls (n = 9) (25 +/- 3 pmol h-1 per 10(6) MNL vs 27 +/- 4 pmol h-1 per 10(6) MNL). These results suggest that there are not systemic changes in this enzyme in CF. The increased metabolic clearance of SMX may therefore be related to factors other than alterations in the level of activity of the N-acetyltransferase NAT1.

4-Aminobenzoic Acid↗
PubMedDate not supplied

A radiometric method for objectively screening large numbers of compounds against Pneumocystis carinii in vitro.

A relatively simple method is reported for accurately quantitating the incorporation of [3H]para aminobenzoic acid (pABA) into the folates of Pneumocystis carinii cultured in vitro, and the subsequent development of a highly sensitive and reproducible 96-well microtitre plate drug screening system. Incorporation of [3H]pABA under optimized conditions has been utilized as a selective indicator of the in vitro viability of P. carinii against which the inhibitory effects of potential drugs were quantified. The anti-Pneumocystis agents pentamidine, sulfamethoxazole, 566C80 and piritrexim gave median inhibitory concentration values of 7.3, 0.1, 1.4 and approximately 100 microM, respectively in this assay. The results suggest that this 96-well plate P. carinii [3H]pABA-incorporation system is suitable as a rapid high throughput primary in vitro screen for detecting compounds with anti-Pneumocystis activity.

4-Aminobenzoic Acid↗
PubMed1991

Bacterially synthesized folate in rat large intestine is incorporated into host tissue folyl polyglutamates.

Unlike mammalian tissues, certain intestinal microflora are capable of de novo synthesis of folate. To explore the availability of bacterially synthesized folate to the host organism, we used [3H] p-aminobenzoic acid (3H PABA) to label folate newly synthesized by the intestinal microflora. Labeled folates were isolated by affinity chromatography and identified by ion-pair HPLC. In this study [3H]PABA was injected into rat cecum to determine whether the [3H]folate synthesized by bacteria appeared in rat liver and other tissues. Rats were kept in sling suits to prevent coprophagy. Ion-pair chromatography of the purified liver folate demonstrated that bacterially derived [3H]folate was incorporated into all host liver-specific folate polyglutamates, mostly penta- and hexaglutamyl derivatives. Similar results were observed in kidney folates. These data provide direct evidence that some of the folate synthesized by the microflora in the rat large intestine is incorporated into the tissue folate of the host.

4-Aminobenzoic Acid↗