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Biomedical subjects

M M Wick

Publications and source records attributed to M M Wick.

62 records · Page 4Linked to original sources
PubMed1977

L-dopa: selective toxicity for melanoma cells in vitro.

In a study of the effect of L-dopa, an intermediate in the biosynthesis of the pigment melanin, on the growth of human and murine melanoma cells a highly selective inhibition of growth was observed for pigmented cell lines (S91A and human melanoma) as compared to the nonpigmented control cells (amelanotic melanoma S91B, mouse fibroblast L929, and Chinese hamster ovary). There was a correlation between toxicity and the extent of incorporation of radioactively labeled L-dopa by each line.

Cell Division↗
PubMed1977

Reduction of streptozotocin toxicity by 3-O-methyl-D-glucose with enhancement of antitumor activity in murine L1210 leukemia.

3-O-Methyl-D-glucose (3-OMG), a nontoxic nonmetabolizable derivative of glucose, is effective in reducing the toxicity of streptozotocin (SZ). In mice the administration of 3-OMG prior to SZ increased the dose that killed 50% of the animals from 240 to 340 mg/kg. Furthermore, the combination of 3-OMG plus nicotinamide (also effective in reducing SZ toxicity) increased the dose that killed 50% of the animals to 540 mg/kg. In L1210 leukemic mice treated with SZ, there was a 2-fold increase in the median survival of animals pretreated with 3-OMG and a 3-fold increase in that of animals pretreated with the combination of 3-OMG and nicotinamide. Neither 3-OMG nor nicotinamide alone enhanced the survival of the leukemic mice. Pretreatment of normal mice with 3-OMG partially prevented the expected fall in hepatic nicotinamide adenine dinucleotide content. This study suggests that 3-OMG, by protecting normal tissue, will permit the administration of larger therapeutic doses of SZ in leukemic L1210 mice. The protective effect of 3-OMG against SZ toxicity appears to be partially mediated through conservation of the nicotinamide adenine dinucleotide content in the tissue.

Animals↗
PubMed1977

Selective incorporation of L-3,4-dihydroxyphenylalanine by S-91 Cloudman melanoma in vitro.

The incorporation of precursors of the biopigment melanin into melanotic and amelanotic S-91 Cloudman melanoma, mouse fibroblast L-929, and Chinese hamster ovary cells was studied. Tyrosine did not selectively accumulate in pigmented cells compared to that in nonpigmented control cells. Inhibition of protein synthesis with cycloheximide provided an estimate of the partition of tyrosine between protein (95%) and pigment biosynthesis (5%). L-3,4-Dihydroxyphenylalanine, a more proximal precursor of melanin, was selectively incorporated into pigmented cells up to 60 times that of control lines. alpha-Melanocyte-stimulating hormone and theophylline, agents that enhance pigmentation, further increased the incorporation of L-3,4-dihydroxyphenylalanine into melanocytic cells. A unique property of melanoma cells thereby has been defined that may permit a selective chemotherapeutic and diagnostic approach.

Cells, Cultured↗
PubMedDate not supplied

Bowen's disease.

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Aged↗
PubMedDate not supplied

Effects of tyrosinase activity on the cytotoxicity of 3,4-dihydroxybenzylamine and buthionine sulfoximine in human melanoma cells.

The rationale for melanoma specific dihydroxybenzene containing antitumor agents is based in part upon the ability of the enzyme tyrosinase to oxidize these pro drugs to toxic intermediates. In situ tyrosinase activity was demonstrated to be affected by both cell density and time from plating in pigmented melanoma cells. Phenylthiourea, which completely inhibited tyrosinase activity with minimal cytotoxicity was found to block the growth inhibitory activity of the antitumor dopamine analog 3,4-dihydroxybenzylamine (3,4-DHBA) (NSC 263475). The antioxidant dithioerythritol was also found to inhibit tyrosinase activity and to block the growth inhibitory effects of 3,4-DHBA in pigmented melanoma cell lines. Buthionine sulfoximine (BSO) was shown to be cytotoxic to melanoma cells and its growth inhibitory effects appears to correlate with tyrosinase levels. Furthermore, BSO was shown to potentiate the growth inhibitory effects of 3,4-DHBA on marginally pigmented human melanoma cell lines.

Antimetabolites↗
PubMedDate not supplied

Bowen's disease.

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Bowen's Disease↗
PubMedDate not supplied

Levodopa and dopamine analogs: dihydroxy and trihydroxybenzylamines as novel quinol antitumor agents in experimental leukemia in vivo.

Levodopa and dopamine demonstrate significant antitumor activity in several experimental systems. We have prepared the nonneurotoxic dihydroxybenzylamine (DHBA) analogs 2,3-DHBA, 3,4-DHBA, and 2,5-DHBA and the trihydroxy derivatives 2,3,4- and 3,4,5-trihydroxybenzylamine. These analogs demonstrated significant and reproducible antitumor activity in the ip P388 and L1210 lymphocytic leukemias. This activity was markedly increased when the drugs were given by multiple injections three times daily for 4 days. 3,4-DHBA and 2,3-DHBA resulted in 30% and 20% long-term survivors, respectively. There was a selective inhibition of thymidine incorporation and a relatively lesser effect on uridine and leucine incorporations. Inhibitory concentrations were between 0.1 and 1.0 mM. The trihydroxy derivatives were more potent, with inhibitory concentrations between 0.01 and 1.0 mM. Furthermore, the trihydroxy derivatives were also able to inhibit the incorporation of uridine and leucine as well as thymidine. The para derivative, 2,5-DHBA, although a potent inhibitor in vitro, was completely inactive in vivo. When L1210 and P388 tumor-bearing animals were given radioactive labeled thymidine in vivo following the administration of drugs. a selective inhibition of thymidine incorporation by tumor cells was observed, with essentially no effect on gut or bone marrow. Doses greater than 200 mg/kg completely suppressed the incorporation of radioactively labeled thymidine by tumor cells 1 hour after administration of drug. A similar dose response was observed in the more slowly growing P388 leukemia, suggesting that the antitumor effect did not strongly correlate with rate of the tumor. Since levodopa and dopamine are currently being evaluated in patients with metastatic melanoma, the availability of analogs with enhanced antitumor activity and broader antitumor spectrum are of interest.

Animals↗