Three centuries of alcohol in the British diet.

Alcoholic drinks were consumed in larger quantities in the eighteenth and nineteenth centuries than in the twentieth century, although there has been a recent increase from the historical low of 1930-60. Beer, spirits and wines once provided at least 2 MJ (nearly 500 kcal) per person per day compared with 0.67 MJ (160 kcal) in 1975, towards an average energy requirement of the total population little different from that needed now. Beer has always contributed most to the alcohol, energy and nutrient content of the diet, although its importance relative to spirits and wine has declined.     

Mice heterozygous for mutation in Atm,the gene involved in ataxia-telangiectasia,have heightened susceptibility to cancer

Ataxia-telangiectasia is characterized by radiosensitivity, genome instability and predisposition to cancer. Heterozygous carriers of ATM, the gene defective in ataxia-telangiectasia, have a higher than normal risk of developing breast and other cancers. We demonstrate here that Atm 'knock-in' (Atm-Delta SRI) heterozygous mice harboring an in-frame deletion corresponding to the human 7636del9 mutation show an increased susceptibility to developing tumors. In contrast, no tumors are observed in Atm knockout (Atm(+/-)) heterozygous mice. In parallel, we report the appearance of tumors in 6 humans from 12 families who are heterozygous for the 7636del9 mutation. Expression of ATM cDNA containing the 7636del9 mutation had a dominant-negative effect in control cells, inhibiting radiation-induced ATM kinase activity in vivo and in vitro. This reduces the survival of these cells after radiation exposure and enhances the level of radiation-induced chromosomal aberrations. These results show for the first time that mouse carriers of a mutated Atm that are capable of expressing Atm have a higher risk of cancer. This finding provides further support for cancer predisposition in human ataxia-telangiectasia carriers.     

An improved method for the collection of large numbers of inseminated eggs ofDrosophila melanogaster

Zusammenfassung Es wird eine verbesserte Methode beschrieben, mit der innerhalb einer Sammelperiode von 3 min etwa 50-100 frisch besamte Eier vonDrosophila melanogaster gewonnen werden können. Verglichen mit den bisher üblichen Sammelperioden von 10, 30 oder mehr min erhält man wesentlich stadienhomogenere Gelege. Eine weitere Verkürzung der Sammelperiode unter 3 min ist wegen der stark abnehmenden Anzahl Eier je Gelege nicht möglich. Vorausgesetzt, dass alle Störungen der Fliegen durch Erschütterungen, Licht, Temperaturschwankungen usw ausgeschaltet werden, können z.B. für strahlenbiologische Experimente zahlreiche 3-min-Gelege im Laufe von 6 oder mehr Stunden gewonnen werden.

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Work supported by Schweizerischer Nationalfonds zur Förderung der wissenschaftlichen Forschung and Jubiläumsfond 1930 der ETH.     

ATM-dependent phosphorylation of nibrin in response to radiation exposure

Mutations in the gene ATM are responsible for the genetic disorder ataxia-telangiectasia (A-T), which is characterized by cerebellar dysfunction, radiosensitivity, chromosomal instability and cancer predisposition. Both the A-T phenotype and the similarity of the ATM protein to other DNA-damage sensors suggests a role for ATM in biochemical pathways involved in the recognition, signalling and repair of DNA double-strand breaks (DSBs). There are strong parallels between the pattern of radiosensitivity, chromosomal instability and cancer predisposition in A-T patients and that in patients with Nijmegen breakage syndrome (NBS). The protein defective in NBS, nibrin (encoded by NBS1), forms a complex with MRE11 and RAD50 (refs 1,2). This complex localizes to DSBs within 30 minutes after cellular exposure to ionizing radiation (IR) and is observed in brightly staining nuclear foci after a longer period of time. The overlap between clinical and cellular phenotypes in A-T and NBS suggests that ATM and nibrin may function in the same biochemical pathway. Here we demonstrate that nibrin is phosphorylated within one hour of treatment of cells with IR. This response is abrogated in A-T cells that either do not express ATM protein or express near full-length mutant protein. We also show that ATM physically interacts with and phosphorylates nibrin on serine 343 both in vivo and in vitro. Phosphorylation of this site appears to be functionally important because mutated nibrin (S343A) does not completely complement radiosensitivity in NBS cells. ATM phosphorylation of nibrin does not affect nibrin-MRE11-RAD50 association as revealed by radiation-induced foci formation. Our data provide a biochemical explanation for the similarity in phenotype between A-T and NBS.