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Biomedical subjects

D Papworth

Publications and source records attributed to D Papworth.

25 records · Page 2Linked to original sources

Murine radiation myeloid leukaemogenesis: relationship between interstitial telomere-like sequences and chromosome 2 fragile sites.

While the specific nature of chromosomal fragile sites and their relationship to human leukaemogenesis remain obscure, there is evidence that chromosomal fragility may, in some circumstances, be associated with telomere-like repeat sequences and that chromosome 2 fragility in the mouse is involved in the initiation of myeloid leukaemia by ionising radiation. Here we describe the molecular cloning and characterisation of two murine telomere-like sequences, one having an inverted repeat structure and the other a simple tandem repeat organisation. The inverted telomere repeat clone generates an in situ chromosome 2 hybridisation pattern very similar to the distribution of the radiation-sensitive fragile sites previously found to be associated with leukaemogenic initiation. Furthermore, statistical comparison of the distributions of radiation induced breakpoints and sites of inverted telomere repeat hybridization indicates concordance at all chromosome 2 sites excluding the terminal regions. These data are discussed with respect to mechanisms of radiation-induced, site-specific chromosome 2 rearrangement and their implications for leukaemogenic initiation.

Acute Disease↗

Murine radiation myeloid leukaemogenesis: a possible role for radiation-sensitive sites on chromosome 2.

There is a paucity of informative data on the potentially important role of specific sites of chromosomal instability in oncogenic processes. Chromosome 2 deletions and rearrangements are known to characterise radiation-induced acute myeloid leukaemia in the mouse. Here we statistically establish a concordance between chromosome 2 breakpoint clusters in these leukaemias and chromosome 2 rearrangements carried at a high in vivo frequency by progeny of irradiated haemopoietic cells. Mechanisms of radiation myeloid leukaemogenesis are discussed with respect to multiple radiation-sensitive sites encoded on chromosome 2 and the possible influence of genomic imprinting on inductive processes.

Alpha Particles↗

Genetic tests for autosomal non-disjunction and chromosome loss in mice.

Two new genetic methods for detecting autosomal non-disjunction and chromosome loss in mice are described. Both methods involve the use of marker genes and Robertsonian translocations, the latter present only in tester parents, to detect events in chromosomally normal mice. With the Rb method, the tester parent carries one or more Robertsonian translocations heterozygously; with the MBH method the tester parent carries two Robertsonian translocations showing monobrachial homology. The high rates of meiotic non-disjunction in the tester mice provide gametes with specific extra or missing chromosomes which, at fertilization, can allow the survival of a proportion of the zygotes lacking or carrying an extra specific chromosome from tested chromosomally normal parents. The Rb method has been assessed for X-ray-induced chromosome 1 loss and non-disjunction in mature oocytes and also for such chromosome 1 loss from the maternal pronuclei of 1-cell zygotes. The MBH method has been assessed for X-ray-induced chromosome 1 loss in male postmeiotic cells and for non-disjunction in spermatocytes. Both methods proved effective in detecting chromosome 1 loss. A single case of the much rarer non-disjunctional event was also found. As applied, both methods compared favourably with the numerical sex chromosome anomaly (NSA) method and have considerable potential for further development.

Animals↗

Risks of radiation at low dose rates.

Cancer mortality has been studied in 1110 women who worked in the U.K. with paint containing radium from 1939 to 1961. Their body contents of radium were small, but they were also irradiated externally by gamma-rays to receive absorbed dose rates of 1-4 mGy per week. Those in the group who were under 30 years of age when they started work show a significantly increased risk of dying from breast cancer. If the excess were due solely to their radiation exposure, it would represent a risk of 20-500 deaths from breast cancer per 10(4) women exposed to 1 Gy, which is consistent with the value used by the International Commission on Radiological Pretection.

Breast Neoplasms↗