Biomedical subjects

L J Ross

Publications and source records attributed to L J Ross.

61 records · Page 4Linked to original sources

PubMedDate not supplied

Screening of potential cancer-preventing chemicals for inhibition of induction of ornithine decarboxylase in epithelial cells from rat trachea.

Sixty-one selected chemicals were evaluated in rat tracheal epithelial (2C5) cells for their capacity to inhibit induction (or inhibit directly) the enzyme ornithine decarboxylase, the activity of which is associated with cell growth and division. a-Difluoromethylornithine (DFMO) was used as a positive control. At non-toxic concentrations, six test compounds had substantial activity (values for IC50 DFMO/IC50 compound >1): N-(2-carboxyphenyl)-all-trans-retinamide, ZK 119010 ¿2-(4-hydroxyphenyl)-3-methyl-1-[6-(1-pyrrolidinyl)hexyl]-1H-indol-5- ol¿, curcumin, 18-a-olean-12-ene-3 ,23,28-triol, genistein and phenethyl isothiocyanate. These should be considered for further development as cancer preventive agents.

Animals↗

PubMedDate not supplied

Screening of potential cancer preventing chemicals as aromatase inhibitors in an in vitro assay.

The inhibition of human placental aromatase was used to rank a series of compounds, with the objective of selecting compounds for further evaluation as chemopreventive agents. (+/-)-p-Aminoglutethimide, introduced over two decades ago as a treatment for breast cancer, had an IC50 of 6.5 microM. Five compounds were more potent than aminoglutethimide in this assay: (+)- vorozole, 4-hydroxyandrostenedione, miconazole nitrate, plomestane, and 4-methoxy-androst-4-ene-3,17-dione. Other compounds with known chemoprevention activity, such as curcumin and genistein, were inactive. This assay for aromatase inhibitors is a rapid, economical way of ranking compounds for further development as chemoprevention agents.

Anticarcinogenic Agents↗

PubMedDate not supplied

Antioxidant activity of michellamine alkaloids.

The alkaloids michellamines A, B, and C are natural products isolated from a Central African tropical plant Ancistrocladus korupensis. We have investigated the radical scavenging ability of these compounds. The alkaloids inhibited the azo-induced oxidation of beta-phycoerythrin with IC50 values in the 0.5- to 0.8-microM range. Michellamine B also protected rat liver mitochondria against lipid peroxidation induced by adenosine diphosphate and Fe2+. The alkaloids were more potent antioxidants in these assays than several compounds being considered clinically as chemoprevention agents.

Animals↗

PubMedDate not supplied

Glycoprotein gD of MDV lacks functions typical for alpha-herpesvirus gD homologues.

Glycoprotein D (gD) belongs to family of conserved structural proteins of alpha-herpesviruses. During productive infection of cells by herpes simplex virus 1 (HSV-1) gD has several important functions, is involved in virus penetration to and release from infected cells and is one of main targets of neutralizing antibodies. Similar functions are shared also by other alpha-herpesvirus gD homologues. Surprisingly, in previous studies it was found that MDV gD expression could not be detected during infection in vitro using immunological methods. In this study we have analyzed expression of MDV gD and its biological consequences. In vitro expression using rabbit reticulocyte lysate and/or overexpression in transfected cells showed that the second ATG codon is required for synthesis of mature, glycosylated gD. In addition, it was found that gD overexpression is neither toxic for transfected cells nor is involved in membrane fusion. After MDV infection of a proprietary cell line stably transfected with plasmid overexpressing MDV gD, no viral particles could be found in culture. On the other hand, cells overexpressing the MDV gD were sensitive to MDV infection in similar way as parental, non-transfected cells. From our study and results of other authors we propound the following conclusions: (i) MDV gD expression is blocked during in vitro infection at transcription level; (ii) MDV gD is lacking many important functions characteristic for other alpha-herpesvirus gD homologues; (iii) overexpression of single MDV gD does not result in production of mature infectious MDV particles.

Amino Acid Sequence↗

PubMedDate not supplied

The 132 bp repeats are present in RNA transcripts from 1.8 kb gene family of Marek disease virus-transformed cells.

Marek's disease virus (MDV) is an oncogenic, lymphotropic herpesvirus of chickens: Loss of its tumourigenic potential is believed to be associated with amplification of the 132 bp repeats from BamHI-D and BamHI-H fragments. We prepared cDNA libraries from RPL1 and MSB1 cell line and from the latter we identified a clone which spanned the 132 bp repeats within the BamHI-H fragment. By sequencing and Northern blot analysis we confirmed the presence of the 132 bp repeats. The analysis by PCR made on the total RNA revealed two 132 bp repeats in MDV transcripts from RPL1 and two to three repeats in transcripts from MSB1 cells. These results show that sequences within the 132 bp repeats are transcribed and are not spliced out as previously reported.

Base Sequence↗

PubMedDate not supplied

Screening of potential cancer preventing chemicals for induction of glutathione in rat liver cells.

With BRL 3A hepatocytes, a series of selected, potentially chemopreventive chemicals was evaluated for their capacity to elevate glutathione (GSH) levels. Since sodium selenite consistently increased GSH levels by approximately 70%, it was selected as a positive control. Of 62 test chemicals, eighteen stimulated GSH levels by >30%, but eleven of these had only a modest effect or displayed considerable toxicity. At non-toxic concentrations, seven compounds had substantial activity: black tea extract (decaffeinated), trans-chalcone, N-ethyl-9-cis-retinamide, indole-3-carbinol, dehydroepiandrosterone (DHEA) curcumin and N-(4-carboxyphenyl)retinamide. These should be considered for further development as cancer preventive agents.

Animals↗

PubMedDate not supplied

Screening of potential cancer preventing chemicals as antioxidants in an in vitro assay.

We used an azo-initiated fluorescence assay to rank a series of antioxidants, with the objective of selecting compounds for further evaluation as chemopreventive agents. Trolox was the positive control for the assay and, with an IC50 of 0.50 microM, was more active than any of the other 16 compounds examined. Three compounds, U83836E, glutathione, and purpurgallin, were only slightly less active with IC50's in the 1-3 microM range. Four other compounds were almost as active: protochatechuic acid, N-acetyl-L-cysteine, U74389G, and lipoic acid (reduced). This fluorescence-based assay for antioxidant activity is a rapid, economical way of ranking antioxidants for further development in the National Cancer Institute's chemoprevention program.

Anticarcinogenic Agents↗