Molecular action of the l(2)gl tumor suppressor gene of Drosophila melanogaster.

Tumor suppressor genes act as recessive determinants of cancer. These genes contribute to the normal phenotype and are required for regulating cell growth and differentiation during development. Inactivation of tumor suppressor genes leads to an unrestricted pattern of growth in specific cell types. In Drosophila, a series of genes have been identified that cause tissue-specific tumors after mutation. Of these, the lethal(2)giant larvae (l(2)gl) gene is the best studied. Homozygous l(2)gl mutations cause the development of malignant tumors in the brain and the imaginal discs. Genomic DNA from the l(2)gl locus has been cloned, introduced back into the genome of l(2)gl-deficient animals, and shown to reinstate normal development. The nucleotide sequence of the l(2)gl gene has been determined, as well as the sequences of two classes of transcripts. Analysis of the spatial distribution of both l(2)gl transcripts and proteins revealed that during early embryogenesis the l(2)gl gene is uniformly expressed in all cells and tissues. In late embryos, the l(2)gl expression becomes gradually restricted to tissues presenting no morphological or neoplastic alteration in the mutant animals. Further mosaic experiments revealed that l(2)gl gene loss can cause three distinct phenotypes: neoplastic transformation, abnormal differentiation, and normal development. These phenotypes depend upon the extent of gene activity in the stem cells prior to the formation of l(2)gl- clones. These analyses indicate that the critical period for the establishment of tumorigenesis occurs during early embryogenesis at a time when the l(2)gl expression is most intense in all cells.

Visualization of pi- and pi+ stopping density distributions in one and two dimensions.

A technique suitable for mapping pi+/- stopping density distributions in patients or phantoms is described. As a position sensitive detector a multiwire proportional chamber with a slit or a hole collimator in front was applied. Results using a water and a Rando phantom are presented for various momenta and momentum band widths of the pi+/- beam. To our knowledge the two-dimensional visualization of a pi- stopping density distribution was realized for the first time.