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Biomedical subjects

M Castegnaro

Publications and source records attributed to M Castegnaro.

At least 73 records · Page 4Linked to original sources
PubMed1990

Induction of characteristic chromosomal aberrations, particularly X-trisomy, in cultured human lymphocytes treated by ochratoxin A, a mycotoxin implicated in Balkan endemic nephropathy.

Ochratoxin A (OA), a mycotoxin which induces nephropathy and kidney tumours in rats and mice, is a contaminant of food consumed by a population with a high incidence of endemic nephropathy (EN). It was therefore tested in vitro for its ability to induce chromosomal aberrations in human peripheral lymphocytes in a small number of subjects, in the presence or absence of a kidney microsomal metabolic activation system. OA was found to induce aberrations on X chromosomes of similar types to those previously detected in lymphocytes from patients suffering from endemic nephropathy.

Animals↗
PubMed1990

High-performance liquid chromatographic determination of ochratoxin A and its 4R-4-hydroxy metabolite in human urine.

One of the metabolites of ochratoxin A (OA) is 4R-4-hydroxyochratoxin A (4-OH-OA), and the ratio of 4-OH-OA to OA excreted in urine can be linked to the carcinogenic potential of this compound. As further support to the hypothesis that OA can be involved in Balkan endemic nephropathy and the associated urinary system tumours, it was decided to investigate the presence of these two compounds in the urine of affected populations. A sensitive method is described for the determination of the compounds at the 10 ng l-1 level. It involves extraction, two purification steps by column chromatography and high-performance liquid chromatography (HPLC), an analysis by HPLC and a confirmatory test by HPLC after derivatisation.

Balkan Nephropathy↗
PubMed1990

Evaluation of methods for destruction of some alkylating agents.

Destruction procedures for dimethylsulfate (DMS), diethylsulfate (DES), methyl methanesulfonate (MMS), and ethyl methanesulfonate (EMS) have been investigated using treatment by 1 N NaOH, 1 N NH4OH, 1 M Na2CO3, and 1 M Na2S2O3. During the kinetic study of the destruction process, the determination of remaining concentrations of the alkylating agents was performed by the derivatization of p-nitrophenoxide to p-nitroanisole and p-nitrophenetole, which were separated by high performance liquid chromatography. The mutagenic activity of the destruction products was evaluated by the Ames test using Salmonella tester strains TA97, TA98, TA100, and TA102. The kinetics of destruction in every case followed a time-dependent exponential relationship. Solutions of 1 M Na2S2O3 showed the highest capacity for destruction of the four alkylating agents, half-lives of DMS, DES, MMS, and EMS being 0.14 min, 1.26 min, 0.60 min, and 5.26 min, respectively. No mutagenic activity was detected following complete destruction in 1 M Na2S2O3.

Alkylating Agents↗
PubMed1990

32P-postlabelling analysis of DNA adducted with urinary mutagens from smokers of black tobacco.

In order to characterize the tobacco-derived mutagens excreted in the urine of tobacco smokers, 32P-postlabelling techniques were used to examine DNA adducts formed from these mutagens with calf thymus DNA in the presence of a metabolic activation system (rat liver S9, Aroclor 1254-induced, with or without acetyl coenzyme A). Using either nuclease P1 or butanol extraction procedures, four-six and three spots, respectively, were reproducibly found on the autoradiograms in the case of the urine extract from two smokers of black tobacco. Using the urinary extract from a non-smoker, only three faint spots were detected after nuclease P1 enrichment. DNA adducts produced in smokers' urine were then compared with those formed by four N-hydroxyarylamines, N-hydroxy-2-amino-3,8-dimethyl-3H-imidazo[4,5-f]quinoxaline, N-hydroxy-2-amino-3-methyl-imidazo[4,5-f]quinoxaline, N-hydroxy-2-naphthylamine and N-hydroxy-4-aminobiphenyl. Visual inspection revealed that none of the reference aromatic amines contributed to the adduct pattern produced by the urinary mutagen(s). However, primary aromatic amines are mainly implicated as urinary mutagens because: (i) they produce frameshift mutations in Salmonella typhimurium strains, (ii) they are easily extractable with blue cotton and (iii) their mutagenicity is abolished by a nitrite treatment procedure for deamination.

Animals↗
PubMed1990

Are mycotoxins risk factors for endemic nephropathy and associated urothelial cancers?

Evidence supporting a role of mycotoxin, in particular ochratoxin A (OA) and citrinin, in the etiology of Balkan endemic nephropathy (BEN) and associated urinary tract tumours (UTT) is reviewed. Both diseases occur in subjects born and/or living in certain rural areas where home-produced and home-stored stable foods were found to be more frequently contaminated by the OA and citrinin. OA levels in blood and urine from patients with BEN or UTT were higher than in controls. OA and possibly other mycotoxins cause endemic porcine nephropathy, a disease with morphology and clinical course similar to those of BEN. OA was carcinogenic in two rodent species with kidney as a major target organ. Animals and strains phenotype as fast metabolizers of debrisoquine were more susceptible to OA-induced carcinogenicity. Among BEN/UTT patients, a greater proportion of fast metabolizers was reported. Although no epidemiological proof of a direct causal role of mycotoxins in BEN/UTT etiology has been presented, the data accumulated so far indicate a need for prospective studies in which mycotoxins as well as other risk factors should be considered.

Animals↗
PubMed1989

Polymorphic ochratoxin A hydroxylation in rat strains phenotyped as poor and extensive metabolizers of debrisoquine.

1. Dark agouti (DA) and Lewis rat strains, which show a genetic polymorphism for debrisoquine-4-hydroxylation, were treated either with a single dose of ochratoxin A (OA) or for 8 weeks with 5 doses per week. Levels of OA and its 4-hydroxy metabolite (4-hydroxy-OA) excreted in urine were determined. 2. At all doses, the metabolic ratio of OA:4-hydroxy-OA was two to five times greater in DA than in Lewis rats, as was the metabolic ratio of debrisoquine:4-hydroxy-debrisoquine. These results are consistent with our previous findings in vitro that hepatic and renal OA 4-hydroxylase activity is three to four times lower in DA than in Lewis rats. These data give further support to the possible co-segregation of genes regulating OA and debrisoquine 4-hydroxylation.

Administration, Oral↗
PubMed1987

Magnetic semi-permeable polyethyleneimine microcapsules for monitoring of N-nitrosation in the gastrointestinal tract.

Semi-permeable polyethyleneimine (PEI) microcapsules were developed recently for trapping unstable electrophilic products in the gastrointestinal tract. Their N-nitrosation has been investigated in vitro and in vivo in the present study. At acid pH N-nitrosation was found to be linearly dependent on nitrite concentration, without a pH maximum. Up to 70% of the nitrosating agent was converted to N-nitroso products that were retained in the microcapsules and detected by a total N-nitroso assay procedure. Microcapsules prepared with different formulations (in order to vary membrane characteristics) provided a limit of detection in the range 1-10 nmol N-nitrosating agent and were also found to have a different capacity for N-nitrosation. Based on n.m.r. data it seems that such N-nitrosation is favoured by the incomplete protonation of this polyamine at acid pH and that nitrosation occurs at the least hindered secondary amine functions. Microcapsules were administered intragastrically in doses of 2 or 6 million to rats also receiving nitrite in the drinking water and were recovered magnetically from faeces. Relative to the maximum possible yield of N-nitrosated microcapsules that could have been excreted within the first 24 h, the excretion (maximum 4.9%) was found to depend on number of capsules administered and the time of administration relative to access to nitrite. Although performed with only a few animals, these preliminary data indicate a performance possibly superior to existing endogenous nitrosation indicators, and a dual purpose system to trap both nitrosating agents and their direct-acting DNA-damaging N-nitroso products.

Animals↗
PubMed1987

Magnetic semipermeable aqueous polyethyleneimine microcapsules for monitoring N-nitrosating species in the gastrointestinal tract.

Magnetic polyethyleneimine (PEI) microcapsules have been developed for trapping electrophilic intermediates in the gastrointestinal (GI) tract. The N-nitrosation of these microcapsules at acid pH was found to be linearly dependent on nitrite concentration, without a pH maximum and with efficient conversion to N-nitrosated products which were detected by a total N-nitroso assay procedure. The limit of detection is in the range 1-10 nmol N-nitroso compound, depending on microcapsule preparation conditions. Nuclear magnetic resonance (NMR) indicates that such N-nitrosation is favoured by incomplete protonation of the polyamine. Microcapsules administered orally to rats were recovered magnetically from faeces and showed extensive N-nitrosation when nitrite was administered in the drinking-water.

Digestive System↗
PubMed1987

Possible underestimation of nitrosatable amine levels in artificial saliva extracts of children's rubber pacifiers and baby-bottle teats.

Children's pacifiers and baby-bottle nipples from various countries were analysed for their content of N-nitrosamines and nitrosatable amines. Using a method involving extraction with artificial saliva, several nitrosamines including N-nitrosodi-n-butylamine (NDBA), N-nitrosodiethylamine (NDEA), N-nitrosodimethylamine (NDMA) and N-nitrosomorpholine (NMOR) were detected in addition to the three nitrosatable amines dibutylamine (DBA), diethylamine (DEA) and dimethylamine (DMA). Upon nitrosation in artificial saliva, these amines produced not only the related N-nitrosamines but also relatively high levels of the corresponding nitramines--N-nitrodibutylamine (NTDBA), N-nitrodiethylamine (NTDEA) and N-nitrodimethylamine (NTDMA). Thus, both N-nitramines and N-nitrosamines should be measured after nitrosation; otherwise, the method probably underestimates the quantities of nitrosatable amines present in artificial saliva extracts. Whether N-nitramines, some of which have been shown to be both mutagenic and carcinogenic, are formed in the saliva of babies exposed to these products remains to be confirmed.

Cooking and Eating Utensils↗
PubMed1986

Influence of ethyl alcohol on the carcinogenic activity of N-nitrosonornicotine.

The present paper describes an experiment designed to investigate the effects of the combined action of different doses of N-nitrosonornicotine (NNN) and ethyl alcohol in BDVI rats. Dose-response relationships of NNN was clearly shown. Ethyl alcohol did not appear to increase, to a great degree, the tumour incidence of NNN. However, ethyl alcohol did shorten the tumour latency period in the groups given NNN in alcoholic solution. In addition, an infiltration of the olfactory tumours to the brain was observed more frequently in both males and females given the high dose of NNN in alcoholic solution.

Animals↗
PubMed1986

Oxidative destruction of hydrazines produces N-nitrosamines and other mutagenic species.

As part of the joint International Agency for Research on Cancer-National Cancer Institute program for the evaluation and development of methods for the degradation of chemical carcinogens, four oxidative techniques for the degradation of hydrazines were investigated. The oxidizing agents used were as follows: sodium hypochlorite, calcium hypochlorite, potassium iodate, and potassium permanganate in sulfuric acid. In each case, at least 99% of the hydrazine initially present was destroyed; however, the potential usefulness of these methods was compromised by the formation (in some reaction mixtures) of carcinogenic N-nitroso compounds and/or unknown mutagenic species. Oxidative degradation of hydrazines is recommended only for the decontamination of glassware and for the treatment of spills, for which reductive degradation methods are not suitable.

Animals↗
PubMed1985

Destruction of aromatic amines in laboratory wastes through oxidation with potassium permanganate/sulfuric acid into non-mutagenic derivatives.

Nine aromatic amines, i.e., benzidine; o-tolidine; o-dianisidine; 3,3'-dichlorobenzidine; 4-aminobiphenyl; 1- and 2-naphthylamine; 4,4'-methylene bis(2-chloroaniline) and m-toluenediamine, were oxidized with potassium permanganate/sulfuric acid. Experimental conditions for complete degradation of these aromatic amines are described. The disappearance of the parent compound through oxidation was measured using HPLC coupled with UV spectrophotometry. The corresponding degradation products were found to be non-mutagenic to Salmonella typhimurium strains TA100, TA98 and TA97, both in the presence and absence of a rat liver S9 activation system. A collaborative study, involving 11 laboratories, has shown the applicability and the reproducibility of this degradation method.

Amines↗
PubMed1984

Volatile nitrosamines in the main stream smoke of black tobacco.

The cigarettes studied are smoked through an automatic device. The mainstream smoke is trapped in Citrate-Phosphate buffer pH 4.5 containing 20 mM ascorbic acid. The volatile nitrosamines are extracted in dichloromethane, purified on alumina column, then analysed by gas-chromatography with a thermal energy analyzer (TEA) detector. The two main volatile nitrosamines quantified are: Nitrosodimethylamine and Nitrosopyrrolidine.

Nitrosamines↗