Key stages in mammary gland development: The mammary end bud as a motile organ

In the rodent, epithelial end buds define the tips of elongating mammary ducts. These highly motile structures undergo repeated dichotomous branching as they aggressively advance through fatty stroma and, turning to avoid other ducts, they finally cease growth leaving behind the open, tree-like framework on which secretory alveoli develop during pregnancy. This review identifies the motility of end buds as a unique developmental marker that represents the successful integration of systemic and local mammotrophic influences, and covers relevant advances in ductal growth regulation, extracellular matrix (ECM) remodeling, and cell adhesion in the inner end bud. An unexpected growth-promoting synergy between insulin-like growth factor-1 and progesterone, in which ducts elongate without forming new end buds, is described as well as evidence strongly supporting self-inhibition of ductal elongation by end-bud-secreted transforming growth factor-β acting on stromal targets. The influence of the matrix metalloproteinase ECM-remodeling enzymes, notably matrix metalloproteinase-2, on end bud growth is discussed in the broader context of enzymes that regulate the polysaccharide-rich glycosaminoglycan elements of the ECM. Finally, a critical, motility-enabling role for the cellular architecture of the end bud is identified and the contribution of cadherins, the netrin/neogenin system, and ErbB2 to the structure and motility of end buds is discussed

Key stages in mammary gland development: the mammary end bud as a motile organ.

In the rodent, epithelial end buds define the tips of elongating mammary ducts. These highly motile structures undergo repeated dichotomous branching as they aggressively advance through fatty stroma and, turning to avoid other ducts, they finally cease growth leaving behind the open, tree-like framework on which secretory alveoli develop during pregnancy. This review identifies the motility of end buds as a unique developmental marker that represents the successful integration of systemic and local mammotrophic influences, and covers relevant advances in ductal growth regulation, extracellular matrix (ECM) remodeling, and cell adhesion in the inner end bud. An unexpected growth-promoting synergy between insulin-like growth factor-1 and progesterone, in which ducts elongate without forming new end buds, is described as well as evidence strongly supporting self-inhibition of ductal elongation by end-bud-secreted transforming growth factor-beta acting on stromal targets. The influence of the matrix metalloproteinase ECM-remodeling enzymes, notably matrix metalloproteinase-2, on end bud growth is discussed in the broader context of enzymes that regulate the polysaccharide-rich glycosaminoglycan elements of the ECM. Finally, a critical, motility-enabling role for the cellular architecture of the end bud is identified and the contribution of cadherins, the netrin/neogenin system, and ErbB2 to the structure and motility of end buds is discussed

Radiobiological Evaluation of Immigrants from the Vicinity of Chernobyl

Eighty individuals (55 adults and 25 children) who were residents of four cities (Kiev, Mozyr, Gomel and Bobrujsk) located 100± 200 km from Chernobyl at the time of the accident in 1986 were tested after immigrating to the US from 1989–1991. A whole-body counter was employed to quantitate radiocesium content. In addition, two biological measures of radiation effects, namely, chromosomal integrity using the micronucleus assay and somatic mutation analysis of erythrocytes at the glycophorin A (GPA) locus, were applied to this group. Radiocesium activity in the body ranged from 0 to 56.8 Bq/kg with a mean and standard deviation of 5.0 ± 8.2 and a median value of 2.0 Bq/kg. Mean radiocesium content by groups was highest in adult males (9.0 ± 11.7; range 0.21–56.8 Bq/kg) followed by adult females (3.3 ± 4.5; range 0–2. ́3 Bq/kg), male children (3.0 ± 5.7; range 0–20.2 Bq/kg) and lowest in female children (1.6 ± 3.5; range 0–12.7 Bq/kg). Individuals with the highest radiocesium content in each group belonged to one family that lived in Mozyr (100 km from Chernobyl) until emigrating in 1989. The frequency of lymphocyte micronuclei and erythrocyte GPA allele- loss (é /N) somatic mutations were both significantly correlated with radiocesium content (r=0.57, p=0.002; r=0.75, p=0.002, respectively). The micronucleus frequency also correlated with the estimated internal absorbed dose from radiocesium in a subset of 20 immigrants for whom this calculation was possible (r=0.71, p=0.0005). Altogether, the biomonitoring data indicate that some subjects had radiation doses sufficient to produce gene and chromosomal mutations in blood cells, although these affects cannot be attributed solely to radiocesium exposure