DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis

During the evolution of cancer, the incipient tumour experiences 'oncogenic stress', which evokes a counter-response to eliminate such hazardous cells. However, the nature of this stress remains elusive, as does the inducible anti-cancer barrier that elicits growth arrest or cell death. Here we show that in clinical specimens from different stages of human tumours of the urinary bladder, breast, lung and colon, the early precursor lesions (but not normal tissues) commonly express markers of an activated DNA damage response. These include phosphorylated kinases ATM and Chk2, and phosphorylated histone H2AX and p53. Similar checkpoint responses were induced in cultured cells upon expression of different oncogenes that deregulate DNA replication. Together with genetic analyses, including a genome-wide assessment of allelic imbalances, our data indicate that early in tumorigenesis (before genomic instability and malignant conversion), human cells activate an ATR/ATM-regulated DNA damage response network that delays or prevents cancer. Mutations compromising this checkpoint, including defects in the ATM-Chk2-p53 pathway, might allow cell proliferation, survival, increased genomic instability and tumour progression.     

Potassium uptake by cold-resistant mouse L cells stored at low temperature

Adaptation of a cultured mouse L cell population to 4 degrees C increased the survival of the cells and induced the uptake of potassium from the medium at this temperature.     

Diagnostic value of human cytomegalovirus DNA PCR regarding different clinical specimens

Conclusions In transplant recipients, a positive HCMV PCR in PBLs is a sign of the possible development of HCMV disease which should be confirmed by further diagnostic approaches. However, detection of HCMV DNA in the CSF appears to be a specific marker of pathological processes, exemplified in a case of HCMV encephalitis.     

Preimplantation mouse embryos cultured in mouse,rat and human sera: differentiation and sister chromatid exchange

Summary Development of 4-cell and of 8-cell mouse embryos and of morulae and blastocysts is inhibited in vitro by mouse serum but not by rat or human sera which also do not influence sister chromatid exchange in cultured morulae and blastocysts.     

On the glutamine and γ-aminobutyric acid contents of various regions of the cat brain

Résumé Les auteurs ont déterminé par la méthode de la chromatographie à deux dimensions, la teneur en glutamine et en acide -aminobutyrique des différentes parties du cerveau du chat. La concentration la plus élevée de l'acide -aminobutyrique a été trouvé dans l'hypothalamus, tandis que celle de la glutamine a été constatée dans le noyau caudé. Les concentrations les plus basses de ces deux protéines apparaissent dans la substance blanche du cerveau.     

Interactions between α-MSH and sex steroids on the preputial glands of female rats

Résumé L'-MSH stimule la croissance des glandes préputiales de la rate intacte, cet effet est moins marqué après l'ablation des ovaires et s'atténue encore après castration et surrénalectomie ou castration et hypophysectomie. Chez l'animal castré, en doses liminaires, la progestérone accroÎt considérablement la stimulation produite par l'-MSH tandis que la testostérone exerce un effet comparable mais moins accentué. Le synergisme de la progestérone et de l'-MSH est encore observé, mais légèrement réduit, chez l'animal castré et surrénalectomisé ou castré et hypophysectomisé.     

Age-dependent changes of acid mucopolysaccharide excretion patterns in human urine

Zusammenfassung Die sauren Mucopolysaccharide im Harn von 37 Normalpersonen verschiedenen Alters (Säuglinge bis Erwachsene) wurden säulenchromatographisch fraktioniert und einzeln bestimmt.

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This study was supported by a grant from the Deutsche Forschungsgemeinschaft, Bad Godesberg.