PubMed · 6966997
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J Marmelzat, M J Rapaport. 1980. Photodermatitis with PABA.. https://doi.org/10.1111/j.1600-0536.1980.tb05618.x
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The metabolic activation and detoxification pathways associated with the carcinogenic aromatic amines provide an extraordinary model of polymorphisms that can modulate human urinary bladder carcinogenesis. In this study, the metabolic N-acetylation of p-aminobenzoic acid (PABA) to N-acetyl-PABA (NAT1 activity) and of sulfamethazine (SMZ) to N-acetyl-SMZ (NAT2 activity), as well as the O-acetylation of N-hydroxy-4-aminobiphenyl (OAT activity; catalyzed by NAT1 and NAT2), were measured in tissue cytosols prepared from 26 different human bladder samples; then DNA was isolated for determination of NAT1 and NAT2 genotype and for analyses of carcinogen-DNA adducts. Both PABA and OAT activities were detected, with mean activities +/- SD of 2.9 +/- 2.3 nmol/min/mg protein and 1.4 +/- 0.7 pmol bound/mg DNA/min/mg protein, respectively. However, SMZ activities were below the assay limits of detection (< 10 pmol/min/mg protein). The levels of putative carcinogen-DNA adducts were quantified by 32P-postlabeling and averaged 2.34 +/- 2.09 adducts/10(8) deoxyribonucleotide phosphate (dNp). Moreover, the DNA adduct levels in these tissues correlated with their NAT1-dependent PABA activities (r = 0.52; P < 0.01) but not with their OAT activities. Statistical and probit analyses indicated that this NAT1 activity was not normally distributed and appeared bimodal. Applying the NAT1:OAT activity ratios (N:O ratio) allowed arbitrary designation of rapid and slow NAT1 phenotypes, with a cutpoint near the median value. Within each of these subgroups, NAT1 correlated with OAT (P < 0.05); DNA adduct levels were elevated 2-fold in individuals with the rapid NAT1 or NAT1/OAT phenotype. Examination of DNA sequence polymorphisms in the NAT1 gene by PCR have demonstrated that an NAT1 polyadenylation polymorphism is associated with differences in tissue NAT1 enzyme activity; accordingly, NAT1 activity in the bladder of individuals with the heterozygous NAT1*10 allele was 2-fold higher than in subjects homozygous for the putative wild-type NAT1*4 allele. Likewise, DNA adduct levels in the mucosa of the urinary bladder were found to be 2-fold (P < 0.05) higher in individuals with the heterozygous NAT1*10 allele (3.5 +/- 2.1 adducts/10(8) dNp) as compared to NAT1*4 homozygous (1.8 +/- 1.9 adducts/10(8) dNp). Thus, these data provide strong support for the hypothesis that NAT1 activity in the urinary bladder mucosa represents a major bioactivation step that converts urinary N-hydroxy arylamines to reactive N-acetoxy esters that form covalent DNA adducts.(ABSTRACT TRUNCATED AT 400 WORDS)
OBJECTIVE: To examine the distribution of patterns of macronutrient density in relation to obesity. DESIGN: Cross sectional. SETTING: Denmark. SUBJECTS: 323 men and women aged 35-65 years, selected randomly from a larger population sample of Danish adults. MAIN OUTCOME MEASURE: Bias in dietary reporting of energy and protein intake in relation to percentage body fat, assessed by comparison of data from an interview on dietary intake with data estimated from 24 hour nitrogen output, validated by administering p-aminobenzoic acid, and estimated 24 hour energy expenditure. RESULTS: Degree of obesity was positively associated with underreporting of total energy and protein, whereas compared with total energy reported, protein was overreported by the obese subjects. CONCLUSION: Errors in dietary reporting of protein seem to occur disproportionately with respect to total energy, suggesting a differential reporting pattern of different foods. Although, on average, all subjects showed a greater underreporting of energy than of protein, this was most common in the obese subjects. Snack-type foods may be preferentially forgotten when obese people omit food items in dietary reporting. These results seem to agree with the general assumption that obese people tend to underreport fatty foods and foods rich in carbohydrates rather than underreport their total dietary intake. These results may have implications for the interpretation of studies of diet and comorbidities related to obesity.
The reaction of singlet molecular oxygen (1O2) with p-aminobenzoic acid (PABA) is quite rapid. The rate constant for reaction of 1O2 with PABA was measured in buffered aqueous solution by the method of competition kinetics and found to be 8.9 x 10(8) M-1 sec-1. The results of a Stern-Volmer analysis indicate that additional loss of 1O2 does not occur through physical quenching by PABA. Although illuminated PABA solutions are known to form 1O2, it appears that PABA is also a very efficient sink for 1O2.