Sedimentation analysis of conformation changes of circular PM 2 DNA in relation to the ionic strength.
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Biomedical subjects
Publications and source records attributed to M Böttger.
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The reaction of the carcinogen N-methyl-N-nitrosourea with mitochondrial DNA from various rat tissues was examined in vivo and in vitro. After incubation of isolated mitochondria or cell nuclei with N[(14)C]-methyl-N-nitrosourea in vitro and subsequent isolation and purification of the DNA the specific radioactivity of the mitochondrial DNA was 3-7 times that of the nuclear DNA. The incorporation of (14)C into embryonic mitochondrial DNA in vitro was about twice that into the liver mitochondrial DNA. Identical incorporation rates, however, were found for the reaction of isolated mitochondrial DNA or nuclear DNA respectively with N[(14)C]-methyl-N-nitrosourea. After intraperitoneal injection of 43.3-58.5mg of N[(14)C]-methyl-N-nitrosourea/kg body wt. to adult rats the labelling of the mitochondrial DNA was on average 5 times that of the nuclear DNA. A smaller specific labelling was observed for the ribosomal RNA, transfer RNA, and mitochondrial RNA as well as for the mitochondrial protein as compared with the mitochondrial DNA. After hydrolysis of the alkylated nucleic acids with hydrochloric acid, fractionation was carried out on Dowex 50 cation-exchange columns. In most experiments 70-80% of the input (14)C radioactivity was eluted in the 7-methylguanine fraction. The preferential alkylation of the mitochondrial DNA by N-methyl-N-nitrosourea in situ is discussed in connexion with the cytoplasmic-mutation hypothesis of carcinogenesis.
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BACKGROUND: Many primary tumors may cause liver metastases, which are generally treated with surgical resection and/or chemotherapy. After resection of liver metastases in patients with colorectal carcinoma, 5-year survival rates are achieved in 25-38%, and two-thirds of patients will experience recurrent metastases. We examined percutaneous, minimally invasive, laser-induced thermotherapy (LITT) as an alternative outpatient procedure. Local tumor control rate and survival data were analyzed prospectively. METHODS: Between June 1993 and August 2000, 7148 laser applications were performed in 1981 lesions in 705 consecutive patients and 1653 treatment sessions. The complications of the procedure were evaluated by clinical examination and magnetic resonance imaging (MRI) and computed tomography. Local tumor control was evaluated by plain and contrast-enhanced follow-up MRI using T1- and T2-weighted spin-echo and gradient-echo sequences every 3 months after treatment. Cumulative survival times were calculated using the Kaplan-Meier method. RESULTS: The overall rate of complications and side effects was 7.5%. The rate of clinically relevant complications was 1.3%. Local tumor control rate after 3 months was 99.3%; 6 months after laser treatment, plain and contrast-enhanced MRI documented a local tumor control rate of 97.9%. In patients treated with MR-guided LITT for unresectable colorectal liver metastases, the mean survival was 41.8 months (95% confidence interval = 37.3-46.4 months). The 1-year survival rate was 93%, the 2-year survival rate was 74%, the 3-year survival rate was 50%, and the 5-year survival was 30%. In patients treated with LITT for liver metastases from breast cancer, the mean survival was 4.3 years (95% confidence interval = 3.6-5.0 years). CONCLUSION: In patients with liver metastases, local tumor destruction using minimally invasive, percutaneous LITT under local anesthesia results in improved clinical outcomes and survival rates and can be a potential alternative to surgical resection.