Biomedical subjects

M Nothisen

Publications and source records attributed to M Nothisen.

3 recordsLinked to original sources

PubMed2001

Towards synthetic viruses.

Gene delivery is too complex to be performed with a single carrier molecule. Synthetic multicomponent vectors are being designed that mimic key properties of viruses. Some solutions, such as diverting cell-anchoring molecules or the endogenous nuclear import machinery from their normal function, are directly copied from bacteria and viruses. Some other solutions are original ones: monomolecular genome condensation via detergent dimerization or endosome disruption by the proton sponge effect are not exploited by natural cell invaders. All these components, however, still have to be assembled into a unique supramolecular system, an 'artificial virus'.

Animals↗

PubMed2001

Early detection of 2-amino-1-methyl-6-phenylimidazo (4,5-b)pyridine(PhIP)-induced mutations within the Apc gene of rat colon.

A large proportion of human cancers result from exposure of individuals to environmental or occupational carcinogens. The early detection of carcinogen-induced mutations is a prerequisite for the identification of individuals at risk for developing cancer. Short G-rich repetitive sequences have been previously identified as hot-spots for frameshift mutagenesis induced by a large variety of carcinogens belonging to several families of widespread environmental pollutants. In order to test if these sequences, when mutated, might serve as biomarkers for carcinogen exposure, we designed a sensitive PCR-based strategy that allows the detection of rare mutational events within a whole genome. 2-Amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP), the most abundant carcinogenic heterocyclic amine generated in cooked meat, induces mammary and colon carcinoma in F344 rats. About 25% of male rats exposed to 400 p.p.m. PhIP in the diet for >43 weeks present colon tumors with specific -1G mutations within 5'-GGGA-3' sequences of the APC: gene. Using our PCR assay we have assessed the occurrence of such specific events in rats exposed to PhIP for only 1, 2, 4 and 6 weeks. A specific amplification signal was already observed in the 1 week-treated population and increases in a treatment time-dependent manner. These data validate this approach for the early detection of mutations and demonstrate its usefulness for molecular epidemiology and early diagnosis.

Animals↗

PubMed2000

Molecular approach in cancer epidemiology: early detection of carcinogen-induced mutations in a whole genome (Review).

Chronic exposure of organisms to endo- or exogenous genotoxic products results in the accumulation of mutations in the genome and eventually to the development of cancers. Early detection of these mutations would allow the identification of at risk individuals who present a high load of mutations either because of an occupational or environmental exposure, or because of less efficient DNA repair processes. However, highly specific and sensitive assays are required to allow the detection of point mutations in a whole genome. We review a long-term study on the mutagenesis induced in E.coli by an aromatic amide, the N-2-acetylaminofluorene. A major contribution of this work was to reveal the presence of specific mutation hot spot sequences. Taking advantage of this observation, we designed a specific, sensitive and semi-quantitative in vitro assay allowing the detection of carcinogen induced mutations. This assay has been validated in vivo and demonstrate the sensitivity of the technique in early detection of mutations and its usefullness in molecular epidemiology, early diagnostic and prognosis.

2-Acetylaminofluorene↗