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E Ackermann

Publications and source records attributed to E Ackermann.

32 records · Page 2Linked to original sources
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Proteinase activity in malignant human breast cancers and NMU mammary tumours of the rat.

In subcellular fractions of human mammary tumours and NMU tumours of rats proteinase activity was studied by means of the synthetic substrates Bz-dl-arginin-4-nitroanilid (BAPNA) and Bz-dl-arginin-2-naphthyl-amid (BANA). Using the substrate BAPNA enzymatic activity was found to be highest in low speed particulate fractions, whereas in NMU tumours of rats the bulk of the activities could be observed in the high speed supernatant. The substrates BAPNA and BANA were cleavaged enzymatically in human mammary tumours at pH 7 and pH 6, respectively, while in rats the maximum turnover of both substrates changed at value of pH 6.5. Enzyme activity with BAPNA was proved to be resistant to alkaline preincubation in human breast cancer tissue only. On the other hand, the enzymatic cleavage of BANA was completely lost in human as well as in rat tumour specimens under these experimental conditions. It can be concluded from these results that both enzyme activities measured in human malignant mammary tumours, which are known for their invading activity, represent two different proteolytic enzymes with their maximum activity at neutral and acidic pH. Similar enzyme activities are quite different in NMU tumours, which are not invasive.

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Clinical pharmacological aspects of drug toxicity testing.

Drugs are xenobiotics. Absorption, distribution, and elimination depend on their physico-chemical character. Lipophilic drugs are usually inactivated or activated by biotransformation systems. Nearly all metabolic pathways are influenced by drugs. Damage of the DNA includes the possible risk of mutation and inducton of cancer. Severe side-effects of drugs and some drug disasters in the past promoted physicians and legislators to elaborate new guidelines for the safety of drugs for human beings. The different requirements of the guidelines are compared using oral contraceptives as example. The problem in studies of drug metabolism in drug safety evaluation is to find out a species in which drug disposition is nearly identical to that in man, because the rat and the mouse are poor predictors of the human situation. In the future, extensive studies on comparative drug metabolism need to be done. The increasing number of hepatic adenomas and neoplasmas in the past ten years in women taking oral contraceptives initiated studies on metabolism of estrogens. Hydroxylation of ethinylestradiol at C 2 has been shown to be the key to understand the activation to arene oxides which bind covalently to nucleic acids and proteins. This metabolic pathway may explain the potential toxicity and cancerogenicity. This example should stress that drug metabolism is part of drug safety evaluation.

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