Search PubMed⌕ Search

Biomedical subjects

T J Hansen

Publications and source records attributed to T J Hansen.

11 recordsLinked to original sources

Carcinogenesis in rats by cyclic N-nitrosamines containing sulphur.

The effects of chronic exposure to three sulphur-containing heterocyclic N-nitrosamines were determined after repeated oral administration to female Fischer 344 rats. Nitrosothiazolidine did not significantly affect the survival of the rats or the incidence of tumours at a total dose of 3.5 mmol. Nitrosodithiazine, an analogue of nitrosothiazolidine which contains an extra sulphur atom inserted between the carbons of its CH2-CH2 moiety, produced only three tumours (two of the nasal mucosa) in a group of 20 rats at a total dose of 1.75 mmol/rat. Nitrosothialdine, the all-cis 2,4,6-trimethyl analogue of nitrosodithiazine, was a potent carcinogen that significantly shortened the lifespan and produced oesophageal tumours in 70% of treated rats as well as numerous tumours of the tongue and liver; this outcome was unexpected because alpha-methyl substitution in other heterocyclic nitrosamines usually reduces or eliminates tumorigenicity. The results extend the data base on the carcinogenic activity of molecules containing both divalent sulphur and the nitrosamino function. The lack of significant carcinogenicity of nitrosothiazolidine in this study suggests that its presence in the human food supply presents a relatively minor risk.

Animals↗

Methotrexate-anticollagen conjugate inhibits in vitro lens cell outgrowth.

After-cataract, or posterior lens capsule opacification, is an undesirable but common sequela to extracapsular cataract surgery. We are investigating biochemical means to prevent after-cataract formation, which can be applied at the time of the original surgery. Based on similar research efforts in cancer chemotherapy, we have prepared a conjugate of the antimetabolic agent methotrexate with an antibody specific for basement membrane collagen, the major protein in the lens capsule. The conjugate was evaluated using biochemical measurements, and retained both antimetabolic and antibody activities. When the conjugate was applied to bovine posterior capsules in vitro, or in vivo in rabbits, it was an effective inhibitor of lens epithelial cell outgrowth in cell culture.

Animals↗

Ames mutagenicity tests on purified 3-nitropropionic acid.

3- Nitropropionic acid is a toxic compound produced by several moulds involved in food fermentation or spoilage. An impure commercial sample of this compound was previously reported as being mutagenic to Salmonella typhimurium strains TA1535 and TA100. In the present study, a sample from the same lot of 3- nitropropionic acid was mutagenic in strain TA100 without metabolic activation, but this activity was diminished after recrystallization. This sample was not mutagenic in strain TA98, before or after recrystallization. A new, purer commercial sample was non-mutagenic in strains TA98, TA100 and TA1538, with or without metabolic activation. Therefore the mutagenicity reported to be due to 3- nitropropionic acid was considered to be due to the impurity(ies).

Mutagenicity Tests↗

Reducing nitrosamine contamination in cutting fluids.

In simulated metalworking coolants that contained both nitrite and di- or triethanolamine at pH 9, N-nitrosodiethanolamine formed at an initial rate of 11 or 6 ppm/wk, respectively. This rate was increased on heating the fluids, on acidification or by the addition of paraformaldehyde, 1,3,5-trimethylhexahydro-s-triazine, ferricyanide or ferric ethylenediaminetetraacetate. N-Nitrosodiethanolamine also formed when nitrite-free coolants containing either of the two amines above were exposed to nitric oxide in air. No nitrosamines were detected in fluids containing primary amines in place of the secondary and tertiary amines, except that N-nitrosooxazolidine was formed in the fluid containing monoethanolamine after addition of formaldehyde-releasing agents, and N-nitrosodiethanolamine and N-nitrosomorpholine were found in fluid containing diglycolamine (HOCH2CH2OCH2CH2NH2) after the fluid was heated at 100 degrees C for 48 hr. These data suggest several steps by which nitrosamine formation in commercial cutting fluids might be substantially reduced: avoiding acid-splitting as a disposal procedure; removing nitrite from the fluid and/or scavenging adventitious nitrosating agents; avoiding unnecessary heating; adding preservatives to the diluted fluid rather than to the commercial concentrate; replacing inherently nitrosatable amine additives by substitutes which are resistant to nitrosamine formation; minimizing concentrations of catalytically active metal complexes.

Catalysis↗

N-nitrosation of secondary amines by nitric oxide via the 'Drago complex'.

Diethylamine (DEA) and nitric oxide (NO) form a stable 1:1 complex (DEA/NO) which can be oxidized to N-nitrosodiethylamine (NDEA). Spectroscopic data for the complex are consistent with the ionic structure originally proposed by Drago & Paulik (1960). Attempts to confirm this structure by X-ray crystallography are continuing. Oxidation of DEA/NO to NDEA appears to be effected by an acid-catalysed dissociation to DEA and NO, followed by autoxidation of NO to an N-nitrosating higher oxide of nitrogen.

Chemical Phenomena↗

Compounds formed by treatment of corn (Zea mays) with nitrous acid.

Nitrohexane has been identified as a major product formed following treatment of corn (Zea mays) with nitrous acid. Preliminary evidence suggests that another compound isolated from the nitrosated corn is an unsaturated nitrolic acid. As an aid to the analysis of N-nitro compounds, we have characterized the response of a chemiluminescence detector (Thermal Energy Analyzer) as a function of pyrolysis chamber temperature for several nitrosamines and for an aliphatic C-nitroso compound, an aromatic C-nitro compound, a nitramine and an alkyl nitrite. The response-temperature profiles are valuable in distinguishing among the various compounds and in optimizing the sensitivity of the detector for use in chromatography. Other tests, including photolysis and stability toward nitrite-scavenging reagents, further aid in distinguishing among the various compounds.

Chromatography, Gas↗

Immunoaffinity column coupled with solution fluorometry or liquid chromatography postcolumn derivatization for determination of aflatoxins in corn, peanuts, and peanut butter: collaborative study.

An AOAC/IUPAC (International Union of Pure and Applied Chemistry) collaborative study was conducted to evaluate the effectiveness of an immunoaffinity column for the determination of aflatoxin. The test portion is extracted with methanol-water (7 + 3), filtered, diluted to less than 30% methanol with water, and applied to the affinity column. The column is washed with water and the concentrated aflatoxins are eluted with methanol. Total aflatoxins are determined by solution fluorometry with bromine (SFB), and individual toxins are determined by reverse-phase liquid chromatography with postcolumn derivatization with iodine (PCD). Corn naturally contaminated with aflatoxins, and peanuts, peanut butter, and corn containing added aflatoxins (B1:B2:G1:G2 = 7:1:3:1) were sent to 24 collaborators in the United States, France, Canada, and the Republic of South Africa. Twelve collaborators used the SFB method, 9 used the PCD method, and 3 used both SFB and PCD methods. Twenty collaborators completed the study (10 used the SFB method, 7 used the PCD method, and 3 used both SFB and PCD methods). Test portions were spiked at 10, 20, and 30 ng/g. For SFB analyses, recoveries of total aflatoxins were 123, 105, and 107%, respectively; the relative standard deviation for repeatability (RSDr) ranged from 11.75 to 16.57%, and the relative standard deviation for reproducibility (RSDR) ranged from 10.97 to 33.09%. For PCD analyses, recoveries were 81, 81, and 83%, respectively; the RSDr ranged from 5.20 to 17.22%, and the RSDR ranged from 4.68 to 50.77%. The RSDr for aflatoxins B1 and G1 for spiked test portions ranged from 5.45 to 23.55%, and the RSDR ranged from 4.21 to 57.28%.(ABSTRACT TRUNCATED AT 250 WORDS)

Aflatoxins↗