Enzymatic elimination of O6-ethylguanine from the DNA of ethylnitrosourea-exposed normal and malignant rat brain cells grown under cell culture versus in vivo conditions
✍ Scribed by Nam-Ho Huh; Manfred F. Rajewsky
- Publisher
- John Wiley and Sons
- Year
- 1988
- Tongue
- French
- Weight
- 677 KB
- Volume
- 41
- Category
- Article
- ISSN
- 0020-7136
No coin nor oath required. For personal study only.
✦ Synopsis
The developing rat brain exhibits a pronounced susceptibility to the tumorigenic effect of ethylnitrosourea (EtNU) and an extremely low repair activity for the D N A alkylation product 06-ethylguanine (06-EtGuar -). We have recently found that a collection of malignant neural cell lines originating from prenatal BDIX-rat brain cells were all highly 06-EtGua repairproficient ( 06-EtGuar '). Subcloned lines showed considerable variability of the repair capacity, suggesting instability of the 06-EtGua repair phenotype. Using one of the subcloned lines (BT3Caf) as a model, we show here that BT3Caf cells grown in monolayer culture repair 06-EtGua much more rapidly than those grown in the form of S.C. tumors in BDIX-rats (whereas 04-ethylthymine is not repaired under either condition). Furthermore, normal prenatal BDIX-rat brain cells (06-EtGua'in vivo) gradually acquire an 06-EtGuar + phenotype upon transfer to long-term monolayer culture. The cellular capacity for enzymatic D N A repair is of particular relevance in relation to both the malignant transformation of normal cells and the therapeutic inactivation of cancer cells by DNAreactive drugs. Further analyses are thus required of the molecular mechanisms controlling the expression of D N A repair enzymes as a function of cell differentiation, in terms of the cellular response to altered microenvironmental conditions, and in search for possibilities to reduce the repair capacity of cancer cells.