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Biomedical subjects

D Hoffmann

Publications and source records attributed to D Hoffmann.

At least 361 records · Page 20Linked to original sources
PubMed1979

Alpha-hydroxylation of N-nitrosopyrrolidine and N'-nitrosonornicotine by human liver microsomes.

The environmental carcinogens N-nitrosopyrrolidine (NPYR) and N'-nitrosonornicotine (NNN) were incubated with human liver microsomes to test for the presence of enzymes catalyzing alpha-hydroxylation, which is likely to be an activation mechanism for these compounds. Both nitrosamines underwent alpha-hydroxylation; rates were higher for NPYR than for NNN, as observed in rats. The results indicate that both NPYR and NNN can be metabolically activated by human liver microsomes.

Humans↗
PubMed1979

Tumor initiating activity of 5,11-dimethylchrysene and the structural requirements favoring carcinogenicity of methylated polynuclear aromatic hydrocarbons.

The tumor initiating activities of 5,11-dimethylchrysene and 5-methylchrysene on mouse skin were compared. After initiating doses of 30 microgram or 10 microgram, with promotion by 3 times weekly applications of tetradecanoylphorbol acetate, both compounds were highly tumorigenic, inducing tumors in 70--85% of the treated animals. Since 5,12-dimethylchrysene had previously been shown to be only a weak tumor initiator, these results support the generalization that the structural requirements favoring carcinogenicity among the methylated chrysenes and other polynuclear aromatic hydrocarbons (PAH) are a bay region methyl group and a free peri position, both adjacent to an unsubstituted angular ring.

Animals↗
PubMed1979

Synthesis and mutagenicity of 5,11-dimethylchrysene and some methyl-oxidized derivatives of 5-methylchrysene.

A series of compounds structurally related to the carcinogen and mutagen 5-methylchrysene (1) was synthesized and tested for mutagenicity toward S. typhimurium TA 100. The compounds prepared were 5,11-dimethylchrysene (2), 5-(hydroxymethyl)chrysene (3), 5-(acetoxymethyl)chrysene (4), 5-carbomethoxychrysene (5), 5-(hydroxymethyl)-1,2,3,4-tetrahydrochrysene (6), 5-carbomethoxy-1,2,3,4-tetrahydrochrysene (7), and 5H-chryseno[4,5-bcd]pyran-5-one (31). When tested in the presence of rat liver homogenate, 1 and 2 were active while 3--7 were less mutagenic than 1; 31 was highly mutagenic. The mutagenicity of 1 and 2 contrasts with the low activity of 5,12-dimethylchrysene, which supports the generalization that the structural requirements favoring activity are a bay-region methyl group and a free peri position, both adjacent to an unsubstituted angular ring. The low activity of 3--7 indicates that methyl oxidation is not an important activation process for 1. This agrees with previous studies in which the major proximate mutagen and carcinogen of 1 was identified as 1,2-dihydro-1,2-dihydroxy-5-methylchrysene.

Animals↗
PubMed1979

Tumor-associated immunity in bovine ocular squamous cell carcinoma detected by leukocyte adherence inhibition microassay.

A microplate modification of the leukocyte adherence inhibition (LAI) assay was used with blood leukocytes from cattle with ocular squamous cell carcinomas (OSCC); control groups were cattle with ocular or cutaneous lesions (not carcinoma) and healthy normal cattle. For the assay, saline extracts of OSCC and skin from the same donor, lymphosarcoma, and mastocytoma (M) were used as antigens. Specific LAI reactivity to OSCC extract (but not to skin extract) was detected in 14 of 18 animals with squamous cell carcinoma. One animal with OSCC showed LAI reactivity to OSCC extract, but 1 clinically normal cow had LAI with the M-extract. Leukocyte adherence stimulation reactions with the various antigens were seen in all groups of animals.

Animals↗
PubMed1979

[Late surgical treatment of traumatic rupture of the oesophagus (author's transl)].

The article reports on a 21-year old patient admitted on an in-patient basis after compressed air injury with a severe open craniocerebral lesion, and in whom the diagnosis of rupture of the oesophagus was made two weeks later only. Late surgical management by means of oesophagus suture and sealing of the diaphragm, was successful. The article discusses the symptoms and possibilities of treatment of traumatic rupture of the oesophagus, basing on the present case, and surgical treatment is advocated even if the 48-hour limit has been exceeded.

Adult↗
PubMed1978

Effects of N-nitrosodiethanolamine and 1,1-diethanolhydrazine in Syrian golden hamsters.

N-Nitrosodiethanolamine (NDEA) and 1,1-diethanolhydrazine (DEH) were synthesized and injected subcutaneously weekly in male and female Syrian golden hamsters. The total NDEA dose per hamster was approx. 15 g/kg body wt. applied in either 7 or 27 subdoses. DEH was administered in 78 applications to two groups yielding total doses of 1.1 g and 273 mg/kg body wt. Under these conditions, DEH did not show a specific demonstrable carcinogenic effect. However, within 78 weeks after the first application, 39 out of 56 hamsters treated with NDEA developed tumors. Primarily, neoplasms of the nasal cavity and tracheal tumors were observed, as well as a few hepatocellular adenomas and sarcomas at the injection site. These findings and those of the earlier study on carcinogenicity of NDEA in rats raise concern as to the safety for human consumption or industrial use of products with the potential for forming NDEA.

Animals↗
PubMed1978

Tobacco-specific nitrosamines: formation from nicotine in vitro and during tobacco curing and carcinogenicity in strain A mice.

The formation of tobacco-specific nitrosamines from the major tobacco alkaloid nicotine was examined. Detached leaf tobacco was fed either [2'-14C]nicotine or [2'-14C]nornicotine and air cured. The cured leaf was then analyzed for [2'-14C]N'-nitrosonornicotine ([2'-14C]NNN). The yield of [2'-14C]NNN was 0.007% from nornicotine and 0.009% from nicotine. Because the ratio of nicotine to nornicotine in conventional nicotine-type tobacco is 20-100:1, nicotine is considered to be the major precursor for the carcinogen NNN in tobacco. The formation of other nitrosamines from nicotine in vitro was then studied. Reaction of nicotine with NaNO2 gave rise to NNN, as well as to two other nitrosamines, 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and 4-(N-methyl-N-nitrosamino)-4-(3-pyridyl)butanal (NNA). Analysis of market products revealed the presence of NNK (0.6-24 microgram/g) in chewing tobacco and snuff. The tumorigenic activity of NNN, NNK, and NNA in strain A mice was studied. NNK induced more lung adenomas per mouse than did NNN, whereas NNA was less active than NNN. In addition, two cases of undifferentiated carcinoma of the salivary glands occurred in the NNN experimental groups.

Adenoma↗
PubMed1978

1,2-dihydro-1,2-dihydroxy-5-methylchrysene, a major activated metabolite of the environmental carcinogen 5-methylchrysene.

The metabolic activation of the environmental carcinogen 5-methylchrysene was studied by combining high-pressure liquid chromatographic analysis of metabolites formed in vitro with assays of these metabolites for mutagenic activity toward Salmonella typhimurium. Metabolites were formed by incubation of 5-methylchrysene with the 9000 x g supernatant from Aroclor-treated rat livers. With the use of reverse-phase columns, the metabolites were resolved into nine peaks, A to I. Each peak was collected and tested for mutagenicity with activiation. Significant mutagenic activity was observed primarily in peak E and to a lesser extent in peak D. None of the other metabolites showed significant mutagenic activity. The major mutagenic metabolite (peak E) was identified as 1,2-dihydro-1,2-dihydroxy-5-methylchrysene (7.0% from 5-methylchrysene); Peak D was 7,8-dihydro-7,8-dihydroxy-5-methylchrysene (2.6% from 5-methylchrysene). Other metabolites included 9,10-dihydro-9,10-dihydroxy-5-methylchrysene, 9-hydroxy-5-methylchrysene, 7-hydroxy-5-methylchrysene, 1-hydroxy-5-methylchrysene, and 5-hydroxymethylchrysene. These results indicate that 1,2-dihydro-1,2-dihydroxy-5-methylchrysene is a major proximate mutagen of 5-methylchrysene.

Animals↗