Search PubMed⌕ Search

Biomedical subjects

B Gold

Publications and source records attributed to B Gold.

At least 127 records · Page 7Linked to original sources
PubMed1977

The effect of 1-methoxypropylpropylnitrosamine in Syrian golden hamsters.

The carcinogenicity of the alpha-dipropylnitrosamine (DPN) methyl-ether, 1-methoxypropylpropylnitrosamine (1-MPPN), was investigated in Syrian hamsters for comparison with the effect of the alpha-DPN acetylester, 1-acetoxypropylpropylnitrosamine (1-APPN). It seemed possible that 1-MPPN, 1-APPN and DPN could form a common intermediate. However, contrary to the effect of 1-APPN, no tumors were found at the injection site after subcutaneous 1-MPPN treatment. The main target organ for 1-MPPN was the respiratory tract (as with DPN) and the lungs were greatly affected. In addition, pharyngeal and forestomach tumors occurred, and these were not observed after DPN administration. The results of 1-MPPN treatment, relative to DPN and 1-APPN, are discussed.

Animals↗
PubMed1977

Carcinogenicity of 1-oxopropylpropylnitrosamine (N-nitroso-N-propyl-proprionamide) in Syrian hamsters.

The effect of 1-oxopropylpropylnitrosamine (1-OPPN) was examined in Syrian hamsters. The subcutaneous (s.c.) LD50 was 308 mg/kg b.w. Animals treated s.c. once with a high dose of 1-OPPN had subcutaneous sarcomas and vaginal papillomas. Weekly s.c. injections for life led to high incidences of sarcomas at the injection site. In addition, 1-OPPN had a systemic effect. Neoplasms developed in the nasal cavity, larynx, trachea, lungs forestomach, and vagina. The results are discussed in connection with those found with other DPN derivatives substituted in the alpha-position.

Animals↗
PubMed1977

Local and systemic effects of 1-acetoxypropylpropylnitrosamine in Syrian golden hamsters.

1-Acetoxypropylpropylnitrosamine (1-APPN) was synthesized and its biological effect examined in Syrian hamsters after subcutaneous (s.c.) administration. 1-APPN induced mesenchymal and epithelial neoplasms at the injection sites, as well as epithelial tumors in remote organs. Local neoplasms were a.c. sarcomas, mammary adenocarcinomas and Schwannomas, whereas tumors of the respiratory tract (papillary polyps, papillomas, adenomas, epidermoid carcinomas, and adenocarcinomas) were attributed to a systemic effect as were pancreas duct tumors. Neoplasms which originated in the upper digestive and genital tracts of females (papillomas, epidermoid carcinomas) may be related to a systemic and local effect of 1-APPN.

Animals↗
PubMed1977

Mutagenicity of 22 N-nitrosamides and related compounds for Salmonella typhimurium TA1535.

Twenty-two N-nitrosamides and related compounds, including 14 nitrosoureas, 5 nitrosocarbamates, and one nitrosocyanamide, were tested at various concentrations for mutagenic activity towards Salmonella typhimurium TA1535 without the use of microsomes. The ether-water partition coefficient, solubility in water, and half-life in aqueous solution were also measured. Twenty compounds were mutagenic, with "standard mutagenic concentrations" (i.e. those producing 100 mutants/dish) of 0.0024--6500 micron. Standard mutagenic concentration was negatively correlated with the partition coefficient. Three compounds (ethyl 2-acetoxyethylnitrosocarbamate, nitrosocarbaryl, and methylnitrosobenzamide) were more active than the classic mutagen methylnitrosonitroguanidine. Nitrosocarbamates were at least 50 times more mutagenic than the corresponding nitrosoureas. Nitrosodihydrouracil and propylene-nitrosourea were more active than related compounds. Ethylnitrosocyanamide was 730 times more mutagenic than ethylnitrosourea. Fifteen of the test compounds (of which 14 were mutagenic) had previously been assayed in rats for carcinogenicity, all with positive results.

Amides↗
PubMed1977

Diallylnitrosamine: a potent respiratory carcinogen in Syrian golden hamsters: brief communication.

Diallylnitrosamine (DAN), one of the few nitrosamines tested thus far that has not induced neoplasms in rats, caused a high incidence of respiratory tract tumors in Syrian golden hamsters treated sc with single or weekly doses of the compound. The effect was dose-dependent. The nasal cavity, larynx, and trachea were the most affected by DAN; most drug-induced tumors at those sites were adenocarcinomas and papillary polyps.

Animals↗
PubMed1976

Induction of malignant bone tumors in rats by 1-(2-hydroxyethyl)-1-nitrosourea.

Forty male MRC-W rats were treated chronically with 1-(2-hydroxyethyl)-1-nitrosourea in drinking water (total dose, 330 mg/rat). Fifteen rats (38%) developed osteogenic osteosarcomas or chondrosarcomas of the lower vertebrae. This was the first time that an orally administered organic compound induced a high incidence of these tumors.

Administration, Oral↗
PubMedDate not supplied

Carcinogenicity tests of acetoxymethylphenylnitrosamine and benzenediazonium tetrafluoroborate in Syrian hamsters.

The metabolic activation of the esophageal carcinogen methylphenylnitrosamine (MPhN) via alpha-hydroxylation to hydroxymethylphenylnitrosamine (HO-MPhN) should afford benzenediazonium ion (BDI) as the ultimate electrophilic metabolite. To determine if this proposed activation pathway is accurate, BDI, as its tetrafluoroborate (BF4) salt, was tested by chronic subcutaneous injection and gavage in Syrian golden hamsters. Acetoxymethylphenylnitrosamine (AMPhN), which is rapidly hydrolyzed to HO-MPhN in vivo, was similarly tested by s.c. injection. AMPhN was weakly carcinogenic, while BDI-BF4 did not induce a significant tumor incidence by subcutaneous administration. When orally administered, BDI was inactive. Both AMPhN and BDI-BF4 were mutagenic only in Salmonella typhimurium strain TA1537 without enzymic activation. The parent nitrosamine, MPhN was also mutagenic in TA1537, but only with enzymic activation. The mechanistic and environmental significance of these results are discussed.

Administration, Oral↗
PubMedDate not supplied

The role of nucleophilicity in the ratio of primary to secondary solute-derived products in the decomposition of (1-acetoxypropyl)propylnitrosamine.

The reactions of 1-propanediazotic acid, generated in situ from the hydrolysis of (1-acetoxypropyl)propylnitrosamine (1-APPN), with inorganic halides (X- = Cl-,Br-,I-) were studied in pH 8.0 buffer at 37 degrees C with specific emphasis on the extent of structurally rearranged solute-derived product. There is a direct correlation between the nucleophilicity of the halide and increased total and individual isomeric propyl halide (PrX) products. However, the relative formation of rearranged secondary propyl halide (2-PrX) is inversely proportional to solute nucleophilicity. The extent of isomerization ranges from 28% for Cl- to 13% for I-. In contrast, 2-propanol accounts for 33% of the total solvent-derived propanol yield. It is also demonstrated that the ratio of 1-PrX/2-PrX is inversely related to [X-] for Br- and I-. The data suggest that a nucleophilicity-driven association of the solute with a propanediazonium ion in the transition state leads to both primary and secondary products. The results are also discussed in terms of understanding the solvolysis products and DNA adducts previously observed from the metabolism of dipropylnitrosamine and the hydrolysis of N-propyl-N-nitrosourea.

Bromides↗
PubMedDate not supplied

Reaction of N-(2-chloroethyl)-N-nitrosoureas with DNA: effect of buffers on DNA adduction, cross-linking, and cytotoxicity.

N-(2-Chloroethyl)nitrosoureas (CNU) are clinically used anticancer drugs whose cytotoxicity is associated with the generation of DNA interstrand cross-links. While studying the sequence selectivity for a series of CNU, a dramatic increase in the formation of N7-alkyldeoxyguanosine was observed when Tris buffer was used rather than phosphate or cacodylate buffers. Moreover, the formation of N7-alkyldeoxyguanosine lesions continues in Tris long after all of the CNU has hydrolyzed. These effects are not seen with the monofunctional alkylating analogues, e.g., N-methyl- and N-(2-hydroxyethyl)-N-nitrosourea. In order to determine if the nature of the CNU-mediated DNA damage was altered by Tris, studies were initiated on the following: (1) alkylation of N7-G in end-labeled DNA restriction fragments; (2) covalent modification of DNA with [ethyl-3H]-N-(2-chloroethyl)-N-nitrosourea; and (3) cytotoxicity in L1210 cells. The data presented demonstrate that Tris increases the yield of the "normal" CNU monofunctional cross-linked adducts, i.e., N7-(2-hydroxyethyl)deoxyguanosine, N7-(2-chloroethyl)deoxyguanosine, O6-(2-chloroethyl)deoxyguanosine, and bifunctional adducts, i.e., 1-(deoxycytid-3-yl)-2-(deoxyguanosin-1-yl)ethane and 1,2-bis(deoxyguanosin-7-yl)ethane. In addition, CNU appears to react with Tris to give a long-lived alkylating intermediate that affords large amounts of DNA adducts not seen with CNU in the absence of Tris. However, in vivo toxicity of CNU in L1210 cells is not affected by the presence of Tris, indicating that the reaction pathway(s) responsible for cross-linking is not significantly sensitive to the nature of the buffer.

Alkylation↗
PubMedDate not supplied

The in vitro methylation of DNA by a minor groove binding methyl sulfonate ester.

The preparation of sequence and groove specific DNA methylating agents based on N-methylpyrrolecarboxamide subunits appended with an O-methyl sulfonate ester functionality (MeOSO2(CH2)2-Lex) has previously been described [Zhang, Y., Chen, F.-X., Mehta, P., and Gold, B. (1993) Biochemistry 32,7954-7965]. In contrast to simple methyl sulfonate esters, e.g., methyl methanesulfonate (MMS), which predominantly methylate at 7-guanine, MeOSO2-(CH2)2-Lex affords N3-methyladenine (3-MeAde) as its major adduct. Using competitive ELISA determinations, the methylation at major and minor groove sites in calf thymus DNA by MeOSO2(CH2)2-Lex has been precisely quantitated. The yields of N7-methylguanine (7-MeGua), 3-MeAde, and O6-methyldeoxyguanosine (6-Me-dGuo) are 0.424, 3.195, and 0.0027 mmol of adduct/mol of DNA, respectively, using 10 microM MeOSO2(CH2)2-Lex and 100 microM DNA. This compares to 0.773, 0.072, and 0.0033 mmol of adduct/mol of DNA for 7-MeGua, 3-MeAde, and 6-Me-dGuo, respectively, using MMS. The increase in the yield of 3-MeAde due to the minor groove equilibrium binding properties of MeOSO2(CH2)2-Lex is approximately 40-fold relative to MMS.

Adenine↗