Biomedical subjects
F V Kohl
Publications and source records attributed to F V Kohl.
Relationship between cellular retinoic acid-binding protein and histology of human lung tumors.
Human lung tumors from 28 patients were investigated by sucrose density analysis for the presence of cellular retinoic acid-binding proteins. In the tumor-free lung tissue and in most of the 20 squamous cell carcinoma and in 1 small cell carcinoma specimens tested no specific binding of retinoic acid was detectable, whereas these binding proteins were observed in 5 adeno- and 1 large cell carcinoma. The amount of retinoic acid-binding protein was slightly increased in 1 bronchial adenoma considered to be a semimalignant tumor. These findings suggest that the occurrence of retinoic acid-binding proteins within lung carcinomas may be related to the histological type of lung cancer. Thus, the antineoplastic effects of retinoic acid suspected to be mediated by specific binding proteins are not generally to be expected on lung cancer.
[Drug-induced headache].
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[Combined chemotherapy-radiotherapy study of small cell bronchial carcinoma: chemo-/radiotherapy vs radio-/chemotherapy].
The authors studied the effect of a chemo-/radiotherapy or radio-/chemotherapy on 52 cases of microcellular bronchial carcinoma, classification "limited disease". The survival curves were slightly better for the patients submitted to primary chemotherapy, but the difference was not statistically significant, and the curves coincided again after 18 months. 60 to 80% of the patients had no complaints or only unimportant complaints during more than half of their survival time. In 23 patients with "extensive disease" who received only a symptomatic therapy or a combined palliative chemotherapy, chemotherapy had a slightly better effect, but this was not statistically significant.
Decreased rate of benzo(a)pyrene-induced sister chromatid exchange in fibroblast cultures from patients with lung cancer.
Fibroblast cultures from 29 lung cancer patients including eight familial cases and from 25 healthy controls were investigated. We studied the benzprene-induced sister chromatid exchange (SCE) following incubation in the presence of 150 nM benzo(a)pyrene and found spontaneously increased SCE values in the patients' cells but a reduced response to benzprene as compared to the control cultures. The benzpyrene-induced SCE was positively correlated with both benzpyrene metabolism and DNA adducts in normal control cells but not in the patients' cells. The ratio of benzypyrene DNA adducts and benzpyrene-induced rate of SCE calculated for the individual cell strains exhibited a bimodal distribution with patients' cells, but not with control cells. We speculate that the described differences between patients' and control fibroblasts might reflect a genetic predisposition to the development of lung cancer in about one half of the patients tested.
Benzo[a]pyrene 4,5-oxide. Discrepancy between induction of sister chromatid exchange and binding to DNA in cultured human fibroblasts.
Benzo[a]pyrene 4,5-oxide was covalently bound to DNA of cultured human fibroblasts and caused sister chromatid exchange. The monooxygenase inhibitor alpha-napthoflavone suppressed this induction of sister chromatic exchange, but did not affect binding to DNA. Control experiments with 4-nitroquinoline 1-oxide showed that alpha-naphthoflavone does not inhibit sister chromatid exchange in general. A more likely explanation for the discrepancy between induction of sister chromatid exchange and binding to DNA is that benzo[a]pyrene 4,5-oxide itself can bind to DNA, but this binding does not lead to a significant increase in sister chromatid exchange. However benzo[a]pyrene 4,5-oxide can be oxidized by monooxygenase to yet unknown products which are potent inducers of sister chromatid exchange. An important conclusion from this is that a biological effect such as the induction of sister chromatid exchange may correlate with the exact nature of DNA binding rather than with total binding, to the point where just measuring total binding may be completely misleading if intended to detect the causes of the biological effect.
Interindividual comparison of epoxide hydratase and glutathione S-transferase activities in cultured human fibroblasts.
Epoxide hydratase activity with benzo[a]pyrene 4,5-oxide and glutathione S-transferase activity with 2,4-dinitrochlorobenzene as substrates were determined in cultured fibroblasts from skin biopsies of different donors and from several biopsies of the same donor. Variation of the results from experiment to experiment was reduced by the use of a reference cell strain and expression of the results as activities relative to those of the reference cells. Epoxide hydratase activity varied 2.3-fold in 39 cultures from the same subject (the variation coefficients were 0.22 and 0.15, respectively). The results indicate that, at least in skin fibroblasts, genetically caused interindividual differences in epoxide hydratase activities do not exist or are negligibly small or very rare. Glutathione S-transferase activity varied more in cultures from different donors (variation coefficient = 0.22) than in different cultures from the same donor (variation coefficient = 0.08), but the highest and the lowest activities only differed by a factor of 2.3. No significant differences in either enzyme activity were observed between males, females, subjects without tumours, lung carcinoma bearers and melanoma patients.
Retinoids inhibit 2,3,7,8-tetrachlorodibenzo-p-dioxine-induced activity of benzo[a]pyrene metabolizing enzymes in human diploid fibroblasts.
Retinoids are known to inhibit the substrate mediated enzyme induction of benzo[a]pyrene metabolizing enzymes. Consequently, the effect of two retinoids on the induction of benzo[a]pyrene metabolizing enzymes by the more potent inductor 2,3,7,8-tetrachlorodibenzo-p-dioxine (TCDD) was investigated. The studies were performed with human diploid fibroblasts in culture. Vitamin A palmitate and all-trans-retinoic-acid were found to prevent the TCDD induced increase of benzo[a]pyrene metabolism in a dose-dependent manner. The fact that this effect was immediately reversible makes it unlikely that it was due to non-specific toxic effects. The data suggest that retinoids cause a preferential inhibition of the de novo synthesis of benzo[a]pyrene metabolizing enzymes.
[Therapy of pulmonary heart disease. Physiological and pathophysiological aspects].
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[Tumor prevention by vitamin A: in vitro studies with human cultured fibroblasts (author's transl)].
Following the well established prevention of chemical carcinogenesis by vitamin A in several species of laboratory animals, we performed in vitro studies with human diploid fibroblasts in culture. Vitamin A-palmitate, alltransretinoic acid and the analogue compound Ro 10-9359 were found to reduce the formation of active intermediates following the administration of G3H Benzo(a)pyrene to the cells. This effect which lead to a considerable decrease of alkylated DNA is not based on a direct inhibition of Benzpyrene metabolizing enzymes by the retinoids but by a preferential inhibition of the de novo synthesis of these enzymes. This caused the well known substrate mediated enzyme induction of benzpyrene metabolizing enzymes to cease. From our data we conclude that the mechanism of the cancer protective effect of vitamin A with respect to certain carcinogens is based on an inhibited activation of procarcinogens. This effect can also be expected in human tissues.
Metabolism and formation of DNA adducts of benzo(a)pyrene in human diploid fibroblasts.
Cultured human diploid skin fibroblasts incubated with [G-3H]benzo(a)pyrene yielded about 10 times more H2O-=soluble benzo(a)pyrene metabolites and DNA adducts of stationary growth phase than did proliferating cultures. This increased formation could be blocked by alpha-naphthoflavone. Trichloropropenoxide and cyclohexenoxide, inhibitors of the epoxide hydratase, inhibited predominantly the formation of DNA adducts. Cultures from older individuals formed significantly more benzo(a)pyrene metabolites and DNA adducts, but control cultures from patients with either lung cancer or melanoma did not. The age influence was not apparent when the ratio of DNA adducts to H2O-soluble metabolites was determined for each individual cell line. However, the proportion of DNA-bound material in the cells from patients with lung cancer was significantly increased compared to cells from melanoma patients or healthy individuals.
Retinoids induce sister-chromatid exchanges in human diploid fibroblasts.
Vitamin A palmitate, retinoic acid and an aromatic retinoic acid analogue (Ro 10-9359) induced sister-chromatid exchanges (SCE) in human diploid fibroblasts. The same SCE level was reached with the 3 compounds tested, when the concentration of vitamin A palmitate was 10 times higher than those of retinoic acid and Ro 10-9395. No correlation was found when the dose-related SCE induction of a retinoid was compared with the respective antineoplastic activity as reported by others.
[In vitro studies on the prevention of tumors by means of vitamin A].
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Decreased dipalmitoyllecithin content found in lung specimens from patients with so-called shock-lung.
Lung specimens were obtained from 9 patients with shock lung (adult respiratory distress syndrome), immediately after death, and from 8 controls. They were analysed for phospholipid content anf for fatty acid composition of sphingomyelin and lecithin. We found an elevated phospholipid content in the affected lungs but a decreased dipalmitoyllecithin fraction of total lecithin as indicated by 127% elevated content of oleic acid in lecithin. As a consequence the relation between the palmitic acid and oleic acid moiety of lecithin shifted from 2.32 in the normal lungs to 1.64 in the diseased lungs. Since the content of dipalmitoyllecithin is closely related to the function of the surfactant system we conclude, that the alteration of surfactant function, observed in patients with adult respiratory distress syndrome may be at least in part a result of an altered surfactant metabolism, but we cannot rule out, that the findings represent an epiphenomenon in shock lung.
[Genetics and bronchogenic carcinoma (author's transl)].
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[Metabolism of benzpyrene: inter-individual differences in man and cancerogenicity].
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[Genetic disposition and bronchial carcinoma].
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[The role of cardiac lymph in the transport of enzymes into the blood stream after myocardial infarction (author's transl)].
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