Seliger, H H
The directions of the research program in understanding the dynamics of the natural phytoplankton populations of the Chesapeake Bay, the methodology, the statistical analysis, and the description of the system are parallel to the requirements for environmental impact studies. Results are reported for the following studies: development of instrumentation and the synoptic isopleth methodology for relating the dynamic distributions of natural phytoplankton populations to water circulation patterns; phytoplankton cage experiments for assessment of nutrient dynamics; sub-lethal concentrations and effects of polycyclic aromatic hydrocarbons; and studies on concentration and time kinetics of induction of liver aryl hydrocarbon hydroxylase system in Fundulus heteroclitus by benzopyrene and 3-methyl cholanthrene. (HLW)
Kagan, V.; Novikov, K.; Bogdanova, E.; Prilipko, L.
Incubation of primary culture of hepatocytes was accompanied by spontaneous degradation of cytochrome P-450 (P-450) and by a decrease of its monooxygenase activities. Accumulation of lipid peroxidation (LPO) products also occurred. Addition of LPO inducers (Fe/sup 2 +/-ADP, NADPH) to the medium led to a drastic acceleration of both processes. Synthetic free radical scavengers (butylated hydroxytoluene, 3-hydroxybenzene, alpha-naphthol) prevented LPO activation and protected P-450 against degradation. Phenolic derivatives of 3,4-benzpyrene, formed as a result of its hydroxylation, also had an antioxidant and a protective effect on P-450. Similarly, incubation of human peripheral blood lymphocytes stimulated by PHA resulted in a rapid inhibition of arylhydrocarbon hydroxylase (AHH). In lymphocytes stimulated by PHA and then induced by 3-methylcholanthrene, the sharply increased AHH activity remained unchanged for a long period and no LPO products were accumulated. Exogenous LPO inducers did not either stimulate LPO and were ineffective on the AHH activity. This was due to the presence of 3-methyl cholanthrene phenolic derivatives formed during lymphocytes induction. It is concluded that free radical scavengers could be used as P-450 stabilizers in cell cultures.
Tests aimed at a conditioning of tumours by means of x-ray irradiation and high-frequency hyperthermia. Methyl cholanthrene-induced fibrosarcoma (IMCM) and its transplant version (T-IMCM) produced at the neck of NMRI-mice at a critical localization immediately next to vital organs, served as a test system since it is almost resistant to simple oncolysis. Individual therapy components were compared for their mutual enhancement of efficacy in 16 test groups, and the triple combination (Cl + X-ray + HFH) was tested in relapse application as well. A 2000-R-x-ray irradiation was followed by almost simultaneous 4 min HF heating and i.v. spore administration at 12 h intervals. Assessment criteria were tumour growth, survival rates and times, absence of recidivity and healing, analysis of post-mortem findings and dimension or duration of lyses. In addition, the two tumour types of induction and transplant tumour were compared. The typical course of clostridial oncolysis can be confirmed in principle. Results show that it is possible by means of additional physical methods as were applied, to increase the systemically apathogenic and selective therapy principle of rather negligible oncolysis to over 80% (IMCM) or 97% (T-IMCM). Concerning the MCA fibrosarcoma which is very resistant to clostridial oncolysis in this mouse-tumour model, marked prolongations of survival or healing are possible even in extremely critical localization. In principle, this provides the preconditions for including oncolysis in clinical studies in human medicine. (orig./MG)
Liu, Chunfang; Ma, Zhan; Xu, Songtao; Hou, Jun; Hu, Yao; Yu, Yinglu; Liu, Ruilai; Chen, Zhihong; Lu, Yuan
Embryonic/germ cell traits are common in malignant tumors and are thought to be involved in malignant tumor behaviors. The reasons why tumors show strong embryonic/germline traits (displaced germ cells or gametogenic programming reactivation) are controversial. Here, we show that a chemical carcinogen, 3-methyl-cholanthrene (3-MCA), can trigger the germ-cell potential of human bone marrow-derived cells (hBMDCs). 3-MCA promoted the generation of germ cell-like cells from induced hBMDCs that had undergone malignant transformation, whereas similar results were not observed in the parallel hBMDC culture at the same time point. The malignant transformed hBMDCs spontaneously and more efficiently generated into germ cell-like cells even at the single-cell level. The germ cell-like cells from induced hBMDCs were similar to natural germ cells in many aspects, including morphology, gene expression, proliferation, migration, further development, and teratocarcinoma formation. Therefore, our results demonstrate that a chemical carcinogen can reactivate the germline phenotypes of human somatic tissue-derived cells, which might provide a novel idea to tumor biology and therapy. PMID:24998261
Kanojia, Deepak; Vaidya, Milind M
Human oral cancer is the sixth largest group of malignancies worldwide and single largest group of malignancies in the Indian subcontinent. Seventy percent of premalignant cancers appear from premalignant lesions. Only 8-10% of these lesions finally turn into malignancy. The appearance of these premalignant lesions is one distinct feature of human oral cancer. At present there is dearth of biomarkers to identify which of these lesions will turn into malignancy. Regional lymph node metastasis and locoregional recurrence are the major factors responsible for the limited survival of patients with oral cancer. Paucity of early diagnostic and prognostic markers is one of the contributory factors for higher mortality rates. Cancer is a multistep process and because of constrain in availability of human tissues from multiple stages of oral carcinogenesis including normal tissues, animal models are being widely used, aiming for the development of diagnostic and prognostic markers. A number of chemical carcinogens like coal tar, 20 methyl cholanthrene (20MC), 9,10-dimethyl-1,2-benzanthracene (DMBA) and 4-nitroquinoline-1-oxide (4NQO) have been used in experimental oral carcinogenesis. However, 4NQO is the preferred carcinogen apart from DMBA in the development of experimental oral carcinogenesis. 4NQO is a water soluble carcinogen, which induces tumors predominantly in the oral cavity. It produces all the stages of oral carcinogenesis and several lines of evidences suggest that similar histological as well as molecular changes are observed in the human system. In the present review an attempt has been made to collate the information available on mechanisms of action of 4NQO, studies carried out for the development of biomarkers and chemopreventives agents using 4NQO animal models. PMID:16448841