[en] We identify all contributions to the 1/Q² term in the Bjorken and Ellis-Jaffe sum rules, which include the matrix elements of a spin-2 twist-2 operator, a spin-2 twist-3 operator, and spin-1 twist-4 operator. The matrix elements of the higher twist operators (twist- three and four) contain explicit gluon fields, and can be evaluated in the MIT bag model with novel use of the QCD equations of motion. Together with the information of the sum rules at low energy, we give a Q² variation of the Bjorken and Ellis-Jaffe sum rules, which should be tested at CEBAF

[en] The COG project 2806A (1995), reviewed the On-line Mendelian Inheritance in Man (OMIM) database of genetic syndromes to identify those syndromes, genes, and DNA sequences implicated in some way in the cancer process, and especially in radiogenic cancer risk. The current report describes a recent update of the survey in light of two years of further progress in the Human Genome project, and is intended to supply a comprehensive list of those genetic syndromes, genes, DNA sequences and map locations that define genes likely to be involved in cancer risk. Of the 8203 syndromes in OMIM in 1997 June, 814 are associated, even if marginally, with cancer. Of the 814 syndromes so linked, 672 have been mapped to a chromosome, and 476 have been mapped to a chromosome and had a DNA sequence associated with their messenger RNA (or cDNA) sequences. In addition, 35 syndromes have sequences not associated with map locations, and the remaining 107 have neither been mapped nor sequenced. We supply the list of the various genetic syndromes sorted by chromosome location and by OMIM descriptor, together with all the associated but unmapped and unsequenced syndromes. (author)

[en] UV-induced pyrimidine dimers were excised from the DNA of wild-type and four mutant strains of Ustilago maydis. Excision was partially dose dependent. The kinetics of excision differed in recombination deficient strains (rec 1 and rec 2) from those found in a recombination proficient radiation-sensitive strain (uvs 3). At fluences above 100 J.m^-2 excision was saturated in uvs 3 but not in rec 1 or rec 2. Fluences above 300 J.m^-2 started to saturate excision in wild-type. pol1-1, a temperature-sensitive DNA polymerase mutant, was excision proficient at both the permissive (22deg) and restrictive (32deg) temperatures. Wild-type cells were observed to excise CC before CT or TT in high dose experiments

[en] Mitotic gene conversion was induced in the diploid yeast strain D7.rad6 which lacks error-prone repair and thus does not mutate. Neutrons (14.5 MeV), ⁶⁰Co gamma rays, and 150 kVp X rays delivered under oxic or anoxic conditions were compared for their ability to induce gene conversion. Doses were chosen to minimize cell killing. A lack of induced mutation in this strain at the ilv1-92 allele was confirmed. Gene conversion of the trp5-27/trp5-12 alleles was induced with a linear dose response, and the yield of convertants per gray was significantly enhanced over yields reported previously for a wild-type stain. The relative biological effectiveness (RBE) of neutrons relative to low-LET radiations was found to be about 2.2 for either oxic or anoxic radiation in contrast to wild-type where the oxic RBE was 1.7 and the anoxic RBE 2.7. Absence of the rad6 function was therefore associated with an altered RBE for the conversional end point. The oxygen enhancement ratio (OER) for gene conversion was found to be about 1.7 for all radiations in contrast to the wild type where the OER for neutrons was 1.7, but for low-LET radiations it was 2.7. As repair of ionizing damage in the rad6 strain did not lead to mutation, owing to the loss of error-prone repair, the changes in yield, RBE, and OER were consistent with the hypothesis that some of the lesions processed by wild type to generate mutations could, in the rad6 strain, lead instead to gene conversion

[en] The relative biological effectiveness (RBE) and oxygen enhancement ratio (OER) were determined in the yeast Saccharomyces cerevisiae for the induction of gene conversion (the product of recombinational repair) and mutation (the product of error prone repair) by 14.5-MeV neutrons in comparison with 60Co gamma rays and 150 KVp X rays. Neutron irradiation in oxic or anoxic conditions induced significantly higher yields of convertants and mutants than sparsely ionizing radiations under the same conditions. RBEs for both gene conversion and mutation under anoxia were significantly higher than under oxic conditions. RBEs for mutant induction under anoxia were lower than the RBEs for gene conversion under the same conditions. The data support the hypothesis that the production of lesions leading to the genetic consequences of gene conversion and mutation differ in their dependence upon LET and the presence of oxygen during irradiation, and therefore the two DNA repair processes which produce these end points recognize, at least in part, different classes of damage

[en] Tradescantia Clone 02 data suggests that linear non-threshold dose responses are expected to the lowest doses and dose rates of low linear energy transfer (LET) radiation. This is likely to be true for other living organisms even though Clone 02 is radiation sensitive. It is concluded that Clone 02 is partially defective in the RAD 6 pathway for the repair of DNA interstrand cross-links (ISCL) and other loss of coding damage (LCD), based on its cross sensitivities to EMS and ionizing radiation. Tradescantia Clone 02 data showing linear non-threshold induction of somatic genetic events in part reflects the repair deficiency of this Clone. More DNA damage is repaired by recombinational mechanisms in Clone 02 than would occur in a wild-type strain. Two important classes of DNA lesions are induced by ionizing radiation in DNA - double strand breaks (DSB) which are repaired by recombination mechanisms, and loss of coding information damage (LCD), which is repaired by error prone mechanisms but may also be a substrate for recombinational repair. Based on data from yeast, there are two different repair pathways which deal with these differing lesions with different somatic genetic consequences. From yeast, yield cross sections can be derived and applied to DNA damage and repair in Tradescantia. For Clone 02, per lesion, more visible genetic events are scored than in wild-type strains. In a radiation-derived sub-clone, Clone 0106, which is more variable than Clone 02, even more events occur per lesion. This derivative clone, plus breeding experiments, indicate that Clone 02 is heterozygous, or a 'carrier' for a mutant version of a gene in the Tradescantia RAD 6 repair pathway. Clone 02 is, therefore, much like a Fanconi's anemia carrier in a human population, while the Clone 0106 derivative is much like a homozygous Fanconi's anemia patient, with respect to its response to ionizing radiation damage. Two anomalies in its dose response curves for 'pink' loss of heterozygosity (LOH) events occur because Clone 02 repairs both DSB and LCD by recombination. Clone 02 has a linear dose response for high LET radiation. Starting from the same initial yieId frequency, wild-types have a sublinear response. The sublinear response reflects a smoothly decreasing probability that 'pinks' are generated as a function of increasing high LET dose for wild-type but not Clone 02. This smoothly decreasing response would be expected for LOH in 'wild-type' humans. It reflects an increasing proportion of DNA damage being repaired by non-recombinational pathways and/or an increasing probability of cell death with increasing dose. Clone 02 at low doses and low dose rates of low LET radiation has a linear dose response, reflecting a 1/16 probability of a lesion leading to LOH, relative to high LET lesions. This differential is held to reflect: microdosimetric differences in energy deposition and, therefore, DNA damage by low and high LET radiations; the effects of lesion clustering after high LET on the probability of generating the end wild-types. While no observations have been made at very low doses and dose rates in wild-types, there is no reason to suppose that the low LET linear non-threshold dose response of Clone 02 is abnormal. The importance of the LOH somatic genetic end-point is that it reflects cancer risk in humans. The linear non-threshold low dose low LET response curves reflects either the probability that recombinational Holliday junctions are occasionally cleaved in a rare orientation to generate LOH, or the probability that low LET lesions include a small proportion of clustered events similar to high LET ionization or both. Calculations of the Poisson probability that two or more low LET lesions will be induced in the same target suggest that dose rate effects depend upon the coincidence of DNA lesions in the same target, and that the probability of LOH depends upon lesion and repair factors. But the slope of LOH in Clone 02 and all other strains never approaches the expected slope of predicted for two hit events. This suggests that only particular combinations of coincident LCD and DSB lesions lead, on repair, to LOH. All the evidence suggests that DNA damage induction is linear to the lowest doses. The evidence suggests that even at the lowest doses and dose rates of low LET radiation, there is a constant probability of LOH arising from repair. The effects on cancer risk of this LOH will depend upon the genotype of the individual, and further selective mechanisms which may ameliorate or intensify the effects of the original LOH event. Radiation LOH mechanisms and organismic selective screens can be tested using mice with a defined genetic back-ground, and with genes involved in DNA repair and cancer risk, inactivated or knocked out to produce 'heterozygotes'. By selecting cancers within or outside the selective screen of the immune system the effects of immunological surveillance on the risks associated with LOH of a cancer risk gene can be measured. By knocking out genes in the RAD 52 or RAD 6 pathways, the differential effects of low and high LET radiations, the effects of repair deficiencies on RBE, and dose rate effects can be measured in heterozygotes. The interest in heterozygotes arises because they are expected to be present in the population at approximately four times the square root of the frequency of homozygotes, and because in terms of Knudson's multi-step theory of cancer risk, they have already inherited the first 'hit' from their parents in the form of one abnormal cancer risk gene. Clone 02 is abnormal, but in the same way that a heterozygous carrier of a Fanconi's anemia gene would be. As 1/77 of South African Afrikaans speakers are carriers of a Fanconi's anemia mutant gene, the Clone 02 results can be extrapolated to real human populations. It would, therefore, be expected that real humans would show linear non-threshold radiation-induced LOH and potentially cancer risk. (author)

[en] Previously published research on the epidemiology and molecular basis of genetic or congenital diseases and their occurrence in certain 'ethnic' or isolated populations is discussed to show the significance of consanguinity and 'ethnicity' as contributing factors. A statistical study aiming to correlate malformations with absolutely any environmental factor may miss the significance of defects in a gene pool. This consideration has an obvious significance for the nuclear industry. For example, carriers of Fanconi's anemia appear to have an increased tendency to develop acute myelogenous leukemia. The authors indicate the difficulty in finding a definite molecular basis even for simple Mendelian monogenic disorders such as Tay-Sachs disease. 12 refs., 4 tabs

[en] Gene conversion of two trp5 alleles has been determined in a derivative of strain D.7 of Saccharomyces cerevisiae exposed to 150 kVp X-rays or to ³H β-rays (by suspension in tritiated water). Precautions were taken to ensure that pre- and post-irradiation conditions were similar for X- and β-irradiated sub-sets of the same population. At similar dose rates, stationary phase cells showed a linear dose response to both radiations. When different dose rates of ³H β-rays were delivered, there was no indication of increased induction per unit dose at lower dose rates. The observed yield per unit dose after ³H β-irradiation was slightly less than that obtained with 150 kV/sub p/ X-rays. Further experiments to determine the RBEs in this system are in progress

No abstract available

[en] A series of populations of the D7 strain D7.52a of Saccharomyces cerevisiae was irradiated with 150-kVp x rays while bubbling with either O₂ or N₂. Linear dose responses were observed for all the populations. In O₂, the effects were proportional to dose from 0.01 to 10 Gy. Effects in nitrogen were proportional to dose over the range 0.125 to 50 Gy. The OER for gene conversion in these experiments was 2.5. At the dose rates used (1.03 to 0.034 Gy/min) there was no evidence of a dose-rate effect