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Biomedical subjects

M A Friedman

Publications and source records attributed to M A Friedman.

At least 145 records · Page 8Linked to original sources
PubMed1980

In vitro cell transformation screening of 4 toluene diamine isomers.

2,4-, 2,5-, 2,6- and 3,4-Toluene diamine (TDA) were tested for their ability to enhance the transformation of primary hamster embryo cells (HEC) by Simian adenovirus 7 (SA7) when administered either prior to or after virus inoculation and for their ability to transform secondary HEC. 2,4-TDA was inactive when given prior to SA7, but active if given after. 2,5-TDA was active in both protocols. 2,6-TDA was marginally active if administered before virus and was the most active of the isomers when administered after virus. 3,4-TDA was the most active compound when added prior to SA7, and was also active when given after virus. All the isomers were capable of producing good dose--responses and absolute increases in the number of virus-transformed foci per dish in one or both of the experimental regimens. Each isomer chemically transformed secondary HEC but good dose--responses were rare, and none of the chemicals were active in more than 50% of the 5 or 6 separate tests performed on each.

Adenoviruses, Simian↗
PubMed1980

Tissue distribution and excretion of 2,4-[14C]toluenediamine in the mouse.

The tissue distribution and excretion of 2,4-[14C]toluenediamine was studied in male mice given a single ip dose (1 microCi, 0.667 mg/kg). By 24 h 52% of the administered radioactivity had been excreted in the urine and 22% in the feces. The organs with the highest concentrations of radioactivity were the liver and kidneys. High concentrations of radioactivity were also observed in the gastrointestinal tract. Elimination of radioactivity from the liver, kidneys, and blood was biphasic, with half-lives of 11.7, 9.1, and 12.6 h, respectively, for the slow phases. The dominant route of excretion was via the kidneys; during the first hour after dosing, nearly 50% of the administered radioactivity was recovered in the urine. However, only an additional 2-4% of the dose appeared in the urine during the remaining 23 h of the experiment. By 24 h, only 1.25% of the administered radioactivity has been trapped from the air expired by the animals.

Animals↗
PubMed1980

Therapy of hepatocellular cancer with combined intrahepatic arterial chemotherapy and whole liver irradiation.

Hepatocellular cancer provides an ideal model for studying combined modality chemotherapy and radiation interactions. We have treated 20 evaluable patients. All patients received intrahepatic arterial (IA) 5 FU (10 mg/kg/d continuous infusion times 5 minus 9 d) + Adriamycin (3-5 mg/m(2)/d bolus times 5 minus 7 d), and 1,500 and 2,100 rads whole liver radiation (300 rads/day). Additionally, 3 patients have received IA Mitomycin C (8 mg/m(2)). After this "induction" therapy patients usually received IV Adriamycin + 5FU +/- Mitomycin monthly. Objective regressions occurred in 9/20 (45%) and another 9/20 (45%) and stable disease. Median duration of response is 5+ months (range 1+ to 8 months). Improvement in liver function tests occurred in 11/19, and local symptomatic relief in 12/15. Median WBC nadir = 4,000; platelet nadir = 115,000. Mild anorexia, fever, and nausea were frequent, but no radiation hepatitis has been detected. This program seems to result in significant clinical benefit (subjective and objective) in this refractory neoplasm.

Adult↗
PubMed1979

High-performance liquid chromatography of 2,6- and 2,4-diaminotoluene, and its application to the determination of 2,4-diaminotoluene in urine and plasma.

2,4-Diaminotoluene is used for the production of industrial dyes, and along with the 2,6-isomer, as an intermediate in the production of polyurethane foams. 2,6- and 2,4-diaminotoluene were resolved as sharp peaks by normal-phase high-performance liquid chromatography in 3 min by an acetonitrile-water-saturated chloroform elution solvent (8:2, v/v) with detection by ultraviolet absorbance at 250 nm. The relationship between peak height and amount injected was linear over a range of 0.025-2 microgram for both compounds. Retention times and peak heights were highly reproducible. Detection was very sensitive, allowing quantitation of 1-2 ng of either compound. Quantitative recovery of 2,4-diaminotoluene from spiked urine and plasma samples was obtained by extraction with methylene chloride.

Animals↗
PubMed1979

In vitro mutagenicity and cell transformation screening of caprolactam.

Caprolactam was tested for genetic activity in bacterial and mammalian screens. It was inactive in the following tests: a) Salmonella/microsome mutagenicity; b) Chinese hamster ovary cell mutagenicity (induction of 6-thioguanine mutants); c) Enhancement of SA7 virus transformation of primary hamster embryo cells, when administered before or after virus, and; d) Chemical transformation of secondary hamster embryo cells.

Animals↗
PubMed1979

Role of dimethylnitrosamine-demethylase in the metabolic activation of dimethylinitrosamine.

In vivo administration to rats of the mixed-function oxidase modifiers 3-methylcholanthrene (MC), pregnenolone-16 alpha-carbonitrile (PCN) or beta-naphthoflavnoe (beta-f) inhibits the hepatic microsome-catalyzed in vitro binding of dimethylnitrosamine (DMN) to DNA. This parallels their effect on DMN-demethylase I, regarded to be the sole activating step in DMN carcinogenesis and fails to account for the previously observed anomaly that MC and PCN inhibit, while beta-NF enhances, the hepatocarcinogenic activity of DMN. The in vitro binding of DMN is clearly dependent on microsomes and NADPH, and is strongly enhanced by soluble cytoplasmic proteins; the presence of the latter has no effect. however, on the relative response to pretreatment by the modifiers. In mice beta-NF enhances and PCN inhibits DMN-demethylase I; beta-NF has no effect on either the cytochrome P-450 level or on the LD50, while PCN strongly increases the cytochrome P-450 level but without influencing the LD50. Neither of the two modifiers has any effect in mice on the host-mediated mutagenicity of DMN in a dose-response study, except for the highest dose of DMN (200 mg/kg) where PCN pretreatment significantly enhanced mutagenicity. To account for the anomalous observations, other potential pathways of DMN metabolism have been explored. Whole rat liver nuclei or isolated nuclear membrane fractions contain no DMN-demethylase or diethylnitrosamine-deethylase activity. In a microsomal mixed-function amine-oxidase assay system neither purified enzyme preparations nor whole microsomes catalyze NADPH oxidation in the presence of DMN as substrate. In addition, the purified enzyme does not catalyze formaldehyde production in the DMN-demethylase assay system. Benzylamine, a typical inhibitor of mitochondrial monoamine oxidase (MAO), is a potent inhibitor of DMN-demethylase activity, but microsomes are devoid of MAO activity. Furthermore, purified MAO has no DMN-demethylase activity. The differential effect of modifiers on the carcinogenicity of DMN probably involves pathways other than DMN metabolism.

Biotransformation↗
PubMed1979

In vitro mutagenicity and cell transformation screening of phenylglycidyl ether.

Phenylglycidyl ether (1,2-epoxy-3-phenoxy propane) (PGE) was tested for genetic activity in bacterial and mammalian tests. It was active in the Salmonella/microsome mutagenicity test. Concentration-dependent mutagenicity was demonstrated in S. typhimurium strains TA1535 and TA100 with and without rat S9, but not in strains TA98, TA1537, or TA1538. These results suggest PGE, is a direct-acting mutagen causing base substitutions. Phenylglycidyl ether did not induce 6-thioguanine-resistant mutants of Chinese hamster ovary cells, with or without rat S9, and with or without serum in the medium. Dose-dependent enhancement of SA7 virus transformation of primary hamster embryo cells was observed at concentrations of 1.6 microgram/ml and higher. In addition, this compound was able to chemically transform secondary hamster embryo cells at concentrations of 6.2 micrograms/ml and higher. At a dose of 2500 mg/kg p.o., PGE was active in the host-mediated assay using C57B1/6 X C3H mice and S. typhimurium strain TA1535. This activity represented a positive response in 2 of 5 animals tested. Murine testicular DNA synthesis was not inhibited by oral administration of PGE at 500 mg/kg.

Drug Evaluation, Preclinical↗
PubMed1979

In vitro mutagenicity and cell-transformation screening of N-(2,3-epoxy-propyl)-phthalimide.

N-(2,3-Epoxy-propyl)-phthalimide (EPP) was tested for genetic activity in the Salmonella/microsome mutagenicity test. Concentration-dependent mutagenicity was demonstrated in S. typhimurium strains TA1535, TA1537 and TA100 with and without rat S9. It was inactive in strain TA1538, and active without rat S9 in TA98 at the high dose. EPP induced 6-thioguanine-resistant mutants of Chinese hamster ovary cells in the absence of an exogenous activating system. EPP produced dose-dependent enhancement of SA7 virus transformation of primary hamster-embryo cells, and transformed secondary hamster-embryo cells in a non-dose-related fashion. At a dose of 5 g/kg p.o. or i.m., EPP was inactive in the host-mediated assay using C57Bl/6XC3H mice and S. typhimurium strain TA1535. Murine testicular DNA synthesis was not inhibited by oral administration of EPP at 1000 mg/kg.

Animals↗
PubMed1979

Effects of cannabinoids on L1210 murine leukemia. III. Inhibition of respiration.

The present study was undertaken in an attempt to establish whether or not some of the many biochemical effects of cannabinoids could be explained by inhibition of energy generation. Of particular interest was the relationship of inhibition of DNA synthesis in L1210 murine leukemia cells by certain cannabinoids to possible effects on respiration. In studies using these cells, delta9-tetrahydrocannabinol (delta9-THC) and delta8-tetrahydrocannabinol (delta8-THC) were inactive when tested both in vitro and in vivo. Since these cannabinoids have previously been shown to be inhibitors of DNA synthesis in L1210 cells, there is no necessary relationship between inhibition of the two processes.

Animals↗
PubMed1979

Combined radiotherapy and multidrug chemotherapy for advanced head and neck cancer: results of a Radiation Therapy Oncology Group pilot study.

Between February 1976 and June 1977, 15 patients with advanced inoperable squamous cell carcinoma of the head and neck were entered in a pilot study sponsored by the Radiation Therapy Oncology Group using combined radiotherapy and multidrug chemotherapy. Chemotherapy consisted of cyclophosphamide, vincristine, and bleomycin (during radiotherapy) and cyclophosphamide, methotrexate, and bleomycin (after radiotherapy). At the time of last followup or of death, the disease had been controlled at the primary site in eight of the 15 patients (53%), in the neck in 12 patients (80%), and in all sites in seven patients (47%). Followup time ranged from 2 to 24+ months with a median of 7 months. Acute toxic effects of the combined treatment, primarily enhanced radiation mucositis and infection, were severe, and three patients had fatal complications. Although the combination chemotherapy may have enhanced the tumor response to radiotherapy in some of these patients, treatment morbidity and complications were prohibitive for the treatment program to progress to a randomized trial.

Adult↗