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Biomedical subjects

B Reiss

Publications and source records attributed to B Reiss.

45 records · Page 3Linked to original sources

Effects of chronic ethanol consumption on the metabolism and carcinogenicity of N'-nitrosonornicotine in F344 rats.

The effects of chronic ethanol consumption on the carcinogenicity and metabolism of N'-nitrosonornicotine (NNN) in male F344 rats have been investigated. Groups of 26 to 30 rats were maintained on either a control liquid diet (Groups 1, 3, and 5) or an ethanol-containing liquid diet (Groups 2, 4, and 6) for 4 weeks prior to and during treatment with NNN. The carcinogen was injected s.c. (10 mg/kg, Groups 3 and 4) three times weekly or added to the liquid diet (17.5 mg/liter, Groups 5 and 6). The total dose was 1 mmol of NNN per rat. Control rats (Groups 1 and 2) received s.c. injections of 0.9% NaCl solution. The nasal mucosa was the main target tissue of NNN in Groups 3 and 4, but both the nasal mucosa and esophagus were major target tissues in Groups 5 and 6. In rats treated s.c. with NNN (Groups 3 and 4), ethanol consumption had no effect on the distribution and incidence of nasal cavity tumors. In rats treated with NNN added to the control liquid diet or to the ethanol-containing liquid diet, the number of tumors of the nasal cavity was 18 in Group 5 and 26 in Group 6 (p less than 0.05). In contrast, the number of rats with esophageal tumors was 25 in Group 5 and 20 in Group 6 (p less than 0.05). The effects of ethanol on the enzyme system which activates NNN were studied in rats which had been maintained on an ethanol-containing liquid diet for 4 weeks. Explants of nasal mucosae, lingual mucosae, esophagi , and livers were cultured in vitro with NNN. Nasal mucosae of ethanol-consuming rats had a 1.5-fold higher (p less than 0.05) alpha-carbon-hydroxylating activity than did those of control rats. Activating enzymes in the lingual mucosae, esophagi , and livers were not induced by ethanol. The results show that the increased susceptibility of the rat nasal mucosa to the carcinogenic effects of NNN added to an ethanol-containing diet could be due in part to an induction of activating enzymes by ethanol. However, since chronic ethanol consumption had no apparent effect on the incidence of nasal cavity tumors in rats treated by s.c. injection of NNN, factors other than enzyme induction are important in determining the effects of ethanol on NNN carcinogenicity.

Alcohol Drinking↗

Enhancement of benzo[a]pyrene mutagenicity by chrysotile asbestos in rat liver epithelial cells.

The co-mutagenicity of chrysotile asbestos and benzo[a]pyrene (B(a)P) was studied in adult rat liver (ARL-18) epithelial cells. Exposure to chrysotile alone did not increase the mutant incidence whereas B(a)P was mutagenic. Simultaneous exposure of the cells to chrysotile and B(a)P resulted in an enhanced mutant recovery compared to exposure to either of these substances alone. However, chrysotile did not enhance the mutagenicity of the carcinogen, N-methyl-N'-nitro-N-nitrosoguanidine.

Animals↗

Nucleotide sequence and exact localization of the neomycin phosphotransferase gene from transposon Tn5.

The nucleotide sequence of 1200 bp from the unique region of transposon Tn5 containing the neomycin phosphotransferase gene (neo) was determined, and the location of the neo gene was identified by deletion mutants in a translational reading frame of 792 bp. The derived gene product, an aminoglycoside 3'-phosphotransferase (APH) II, consists of 264 amino acid residues and has a calculated Mr of 29053. Its amino acid sequence shows sequence homologies to the APH type I enzyme coded for by transposon Tn903 (Oka et al., 1981).

Amino Acids↗

Metabolism of N'-nitrosonornicotine by cultured rat esophagus.

The metabolism of N'-nitrosonornicotine (NNN), an esophageal carcinogen, by organ cultured F-344 rat esophagus was investigated. The major metabolites were separated by h.p.l.c. and were identified by comparison to standards as 4-hydroxy-1-(3-pyridyl)-1-butanone, 4-hydroxy-4-(3-pyridyl)-1-butanol and 4-oxo-4-(3-pyridyl)butyric acid from 2'-hydroxylation of NNN and 4-hydroxy-4-(3-pyridyl)-butyric acid from 5'-hydroxylation of NNN. These results demonstrate that alpha-hydroxylation, which leads to electrophilic diazohydroxides, is the major pathway of metabolism of NNN in cultured F-344 rat esophagus. The extents of formation of the metabolites increased with time and the ratio of products resulting from 2'-hydroxylation to those resulting from 5'-hydroxylation was 4.3 after 1 h, 3.9 after 6 h, 3.4 after 24 h and 3.1 after 48 h. F-344 rat liver slices from the same animals produced metabolites of NNN with a 2'/5'-hydroxylation ratio of 1.4. The 2'/5'-hydroxylation ratio in cultured Syrian golden hamster esophagus was 0.3. These results, together with those of parallel studies of NNN metabolism in A/J mouse lung and Syrian golden hamster trachea indicate that among these tissues, F-344 rat esophagus has a unique ability to preferentially hydroxylate the 2'-position of NNN. The results suggest that 2'-hydroxylation is the key step in the metabolic activation of NNN in rat esophagus.

Animals↗

Conditions affecting prolonged maintenance of mouse and rat colon in organ culture.

The effect of variations in culture conditions on survival of fragments of mouse and rat descending colon in organ culture was studied by morphological and functional criteria. A combination of conditions demonstrated to be beneficial permitted maintenance for at least 35 days. These included: a gaseous environment of 95% O2:5% CO2, an attachment matrix consisting of a Metricel GA-4 membrane (pore size, 0.8 mu), intermittent exposure to the gas and fluid phases by rocking in 5 ml medium and supplementation of the medium with 1.0 microM dexamethasone and 10% FBS. During this time, the crypt structure of the mucosal epithelium was well preserved, and DNA synthesis in the crypts and mucin production in the crypts and superficial epithelium continued. In addition, the synthetic trophic hormone, pentagastrin, stimulated DNA synthesis in the mucosal epithelium of mouse colon fragment in short-term organ culture.

Animals↗