A cross-sectional study of self-reported chemical-related sensitivity is associated with gene variants of drug-metabolizing enzymes.

Background: N-acetyltransferases (NAT) and glutathione S-transferases (GST) are involved in the metabolism of several ubiquitous chemical substances leading to the activation and detoxification of carcinogenic heterocyclic and aromatic amines. Since polymorphisms within these genes are described to influence the metabolism of ubiquitous chemicals, we conducted the present study to determine if individuals with self-reported chemical-related sensitivity differed from controls without self-reported chemical-related sensitivity with regard to the distribution of genotype frequencies of NAT2, GSTM1, GSTT1, and GSTP1 polymorphisms.

Methods: Out of 800 subjects who answered a questionnaire of ten items with regard to their severity of chemical sensitivity 521 unrelated individuals agreed to participate in the study.

[Genetic differences in enzymes of folic acid metabolism in patients with lip-jaw-palate clefts and their relatives].

Background: The effectiveness of folic acid supplementation in the periconceptional period for the prevention of cleft lip/cleft lip and palate (CLP) is contradictorily discussed. Genetically determined variants of enzymes of the folic acid metabolism could be part of the key to success or failure of folate supplementation. A mutation of the methylenetetrahydrofolate reductase (MTHFR) gene is suspected to be a risk factor for CLP.

Susceptibility genes: GSTM1 and GSTM3 as genetic risk factors in bladder cancer.

Glutathione S-transferase (GST, E.C. 2.

Gender-specific effects of NAT2 and GSTM1 in bladder cancer.

One approach for risk assessment of cancer is the evaluation of polymorphic enzymes involved in cancer using molecular tools. Phase II enzymes are involved in the detoxification of several drugs, environmental substances and carcinogenic compounds. Here, we analyzed enzymes for their putative relevance in urinary bladder cancer.

Genotyping of the polymorphic N-acetyltransferase (NAT2) and loss of heterozygosity in bladder cancer patients.

Acetylation is one of the major routes in metabolism and detoxification of a large number of drugs, chemicals and carcinogens. Slow acetylators are said to be more susceptible to developing bladder cancer and because of investigations about tumor risk based on phenotyping procedures, it was our aim to study the distribution of allelic constellations of the N-acetyltransferase (NAT2) by genotyping patients with bladder cancer. We analysed NAT2 gene of blood and tumor DNA from 60 patients with primary bladder cancer and DNA of blood samples from 154 healthy individuals.

Regional fine mapping of the multiple-aberration region involved in uterine leiomyoma, lipoma, and pleomorphic adenoma of the salivary gland to 12q15.

Cytogenetic aberrations involving 12q13-15 are frequently observed in a variety of benign solid tumors. Using a chromosome walking approach combined with fluorescence in situ hybridization analysis, we were able to show that the chromosome 12 breakpoints involved in uterine leiomyoma, pleomorphic adenoma of the salivary gland, and lipoma cluster to the same chromosomal region, which we therefore designated MAR (multiple-aberration region). By comparing the G-banding pattern of prometaphase chromosomes of amniotic fluid cells and lymphocytes to the position of hybridization signals obtained with a cosmid pool encompassing this breakpoint hot spot region, MAR was assigned to 12q15.

Melatonin in edible plants identified by radioimmunoassay and by high performance liquid chromatography-mass spectrometry.

Melatonin, the chief hormone of the pineal gland in vertebrates, is widely distributed in the animal kingdom. Among many functions, melatonin synchronizes circadian and circannual rhythms, stimulates immune function, may increase life span, inhibits growth of cancer cells in vitro and cancer progression and promotion in vivo, and was recently shown to be a potent hydroxyl radical scavenger and antioxidant. Hydroxyl radicals are highly toxic by-products of oxygen metabolism that damage cellular DNA and other macromolecules.

Isolation and mapping of a cosmid clone containing the human NAT2 gene.

The NAT2 gene encodes for a polymorphic arylalkylamine N-acetyltransferase and thus accounts for the human N-acetylation polymorphism. By a NAT2-specific primer set we have screened a human chromosome 8-specific cosmid library. A positive cosmid clone was mapped by fluorescence in situ hybridization to 8p22.

Pleomorphic adenoma cells vary in their susceptibility to SV40 transformation depending on the initial karyotype.

Chromosomal aberrations involving 8q12 or 12q13-15 characterize two cytogenetic subgroups of salivary gland pleomorphic adenomas. As the tumors of the two groups differ in their clinical and histologic characteristics, we decided to determine their susceptibility to SV40 transformation. We transfected cell cultures from 13 adenomas with aberrations involving 8q12 and from seven adenomas with involvement of 12q13-15 using an SV40 plasmid coding for the early region of the viral genome.

A recurrent marker chromosome involving chromosome 1 in two mammary tumors of the dog.

An apparently identical marker chromosome resulting from a chromosome 1. translocation was found in the mammary carcinomas of two bitches. Although these karyotypic aberrations were the sole clonal aberrations detected, it was not possible to unambiguously identify the material translocated to the chromosome 1 in either animal.

Pleomorphic adenomas with unbalanced chromosomal abnormalities have an increased in vitro lifetime.

The in vitro lifetime of 100 salivary gland pleomorphic adenomas was investigated. On the average, they had a limited lifetime of 3.7 passages.

Identification of flow-sorted chromosomes by G-banding and in situ hybridization.

The identification of flow-sorted chromosomes is a very important tool for checking the purity of the fractions obtained. An easy and reproducible method for obtaining G-banded chromosomes with good resolution of bands is described. Also, we are able to show that the percentage of chromosomes which can be clearly distinguished by this procedure depends to a large extent on the duration of mitotic arrest.

Structural rearrangements of chromosome Nr 8 involving 8q12--a primary event in pleomorphic ademona of the parotid gland.

Nine pleomorphic adenomas of the human parotid gland were investigated. Within this series the group of cases having clonal aberrations of chromosome Nr 8 predominates. The occurrence of cases with trisomy-8 and cases with structural rearrangements involving a breakpoint in 8q11-8q13 allows a further subdivision of this group of tumors.

Rearrangements of chromosome region 12q13----q15 in pleomorphic adenomas of the human salivary gland (PSA).

Nine of 40 pleomorphic salivary gland adenomas (PSAs) showed clonal aberrations of chromosome 12, with a breakpoint at 12q13----q15. The cytogenetic findings in these cases and those of nine additional cases reported in the literature suggest that this type of aberration is a primary change directly involved in the genesis of PSA.

Inhibition of day time, but not isoproterenol-stimulated pineal N-acetyltransferase activity by an unidentified pineal compound.

Day time rat pineal N-acetyltransferase (P-NAT) activity is higher when homogenate used for incubation is diluted. Samples containing homogenate equivalent to 1/80 pineal gland had highest enzyme activity when compared with samples that contained homogenate equivalent to 1/40 and 1/20 pineal gland, respectively. Thus P-NAT activity is inhibited by a compound present in the pineal gland of the rat.

Interindividual differences of corneal sensitivity. Genetic aspects.

By means of an electronic optical esthesiometer corneal sensitivity was examined in 91 volunteers of different age groups. Additionally, the anesthetic duration of the local anesthetic benoxinate was investigated. Corneal sensitivity decreases with advancing age.

A new banding pattern of human chromosomes by in situ nick translation using ECO RI and biotin-dUTP.

Here we present first results of an attempt to replace the nicking activity of DNAase I by ECO RI for in situ nick translation of human chromosomes. For the detection of nick translated sites we used biotinylated dUTP. The procedure resulted in a distinct banding pattern of the chromosomes which does not seem to correspond to that reached by any known banding technique.

The pipette-method: its application to cytogenetic studies of tumor cells cloned in semisolid media.

A simple method is herein described which allows easy cytogenetic analyses of human tumor cells grown in semisolid media. The quality of the metaphases is relatively good, comparable with that reached by using conventional cytogenetic methods. Therefore, the demonstration of G-, Q-, C-bands, and nucleolus organizing regions (NOR) is possible without any problems.

Further evidence for nonrandom chromosome changes in carcinoma cells--a report of 28 cases.

A cytogenetic study was made of pleural and ascitic effusions from 28 carcinoma patients. Gross chromosome abnormalities were observed in each case. A selection against heteroploid cells occurred generally in long-term cell cultures.

N-acetyltransferase of rat pineal gland acetylates isoniazid.

The tuberculostatic drug isoniazid is acetylated by pineal N-acetyl transferase (P-NAT) of the rat. Kinetics of isoniazid acetylation are different compared to that of serotonin acetylation. Apparent enzyme kinetic parameters for the unstimulated type of P-NAT were: Km: 4.

Cytogenetic observations on two ovarian carcinomas with double minutes, one with a 6q- marker chromosome.

A high number of structurally altered marker chromosomes was found in two cases of ovarian carcinoma. Even by the application of different staining methods it was not possible to identify all the chromosomes. No evidence for the existence of a translocation between chromosomes 6 and 14 was found, which seems to be a specific abnormality characteristic of papillary serous cystadenocarcinomas of the ovary.

Studies on the metabolism of benoxinate by human pseudocholinesterase.

The local anesthetic drug benoxinate (oxybuprocaine, Novesine) is hydrolyzed to 3-butoxy-4-aminobenzoic acid. A rapid and simple spectrophotometric method for benoxinate hydrolysis by human plasma was developed. Benoxinate is hydrolyzed enzymatically by an esterase present in the serum.