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Biomedical subjects

R Waters

Publications and source records attributed to R Waters.

At least 19 recordsLinked to original sources
PubMed1992

The repair of large DNA adducts in mammalian cells.

This paper describes experiments involving the measurement of DNA damage and repair after treatment with 4-nitroquinoline 1-oxide (4NQO) or aflatoxin B1 (AFB1) epoxide in a number of mammalian cell cultures primarily associated with defects in the excision repair of UV-induced DNA damage. The results with transformed derivatives of XP cells belonging to different complementation groups showed that the extent of repair of 4NQO adducts at the N2 or C8 of guanosine did not correlate to the extent of repair reported by others after UV-irradiation. An examination of 4NQO repair in rodent UV-sensitive cell lines from different ERCC groups indicated that again there was little correlation between the extent of 4NQO and UV repair. However, regardless of complementation group those mutants that were defective in the repair of pyrimidine dimers and 6,4-photoproducts did exhibit a reduced ability to repair the 4NQO N2 guanosine adduct, whereas those mutants defective in pyrimidine dimer repair alone were able to repair this lesion as normal. In all of these cell lines there was a normal capacity to repair the 4NQO C8 guanosine adduct. Less extensive experiments involving AFB1 epoxide showed an XPC-transformed cell line was able to repair 40% of lesions after 6 h, whereas only 20% of repair is seen after UV. The rodent mutant V-C4 which belongs to the same ionising radiation group as irs2, was partially defective in repairing AFB1-induced damage. These experiments highlight the fact that although there are many commonalities between the repair of UV damages and lesions classed as large DNA adducts differences clearly exist, the most striking example here being the repair of the C8 guanosine 4NQO adduct which rarely correlates with a defect in UV repair.

4-Nitroquinoline-1-oxide↗
PubMed1992

Sensitivity and single-strand DNA break repair in Chinese hamster mutants exposed to the carcinogen aflatoxin B1 epoxide and its dichloride model.

Aflatoxin B1 (AFB1) is a potent carcinogen and mutagen. It requires metabolic activation to be converted to the DNA-binding product aflatoxin B1 epoxide (AFB1-epoxide). A model of this epoxide is aflatoxin B1 dichloride (AFB1Cl2). Both react at the N7 position of guanine to form large adducts. The major adduct formed can either be rapidly removed to leave an apurinic site or can undergo ring opening of the imidazole ring to form a chemically stable adduct. A number of Chinese hamster DNA repair-deficient mutants have been screened for their sensitivity to AFB1-epoxide and AFB1Cl2. Some of the mutants screened belong to different UV complementation groups. Human genes involved in nucleotide excision-repair correct deficiencies found in these complementation groups. The mutants which were found to be most sensitive to AFB1 (V-C4 and V-H1) were further investigated. Alkaline elution was used to measure AFB1-induced DNA single-strand break repair in the mutants. V-H1 repaired completely in 24 h whereas V-C4 displayed only partial repair.

Aflatoxin B1↗
PubMed1992

Radical axillary dissection in the staging and treatment of breast cancer.

The results of 237 radical axillary dissections undertaken by one surgeon in patients with breast cancer were reviewed to evaluate the role of this procedure in staging and treatment. The accuracy of physical examination in detecting axillary metastases was 68%. With a policy of enforced shoulder immobilisation for 10 days postoperatively, the incidence of postoperative wound complications was 8%. There have been three axillary recurrences during a median follow-up period of 44 months (range 6-97 months). Late complications were assessed in 50 patients followed up for greater than 12 months. While eight patients complained of constant swelling of the arm, only three had a difference in arm circumference of greater than 3 cm and only one had persistent limitation of shoulder abduction. Radical axillary dissection ensures accurate clinical staging and provides excellent local control with few complications and without the need for axillary irradiation.

Axilla↗
PubMed1979

Energy cost of walking of below-knee amputees having no vascular disease.

Fifteen unilateral below-knee amputees with no preexisting vascular disease were studied during free velocity walking to determine energy expenditure with and without a prosthesis. Expired air was collected, and heart rate and respiratory rate data were telemetered. Mean velocity for the unrestrained walking was 71 m/min, both during ambulation with a prosthesis and during crutch walking (without a prosthesis). Heart rates were within normal ranges during prosthetic walking (106 beats/min), but rose significantly to 135 beats/min for crutch walking. Energy cost also rose significantly from a mean of 15.5 ml O2/kg/min with a prosthesis of 22.3 ml O2/kg/min with crutches. The oxygen uptake measured in units of ml O2/kg/m increased when the subjects walked faster or slower than their free cadence. We concluded that the use of the prosthesis should be encouraged and that the amputee should be allowed to choose his natural velocity of walking.

Adult↗
PubMed1979

Overlapping pathways for repair of damage from ultraviolet light and chemical carcinogens in human fibroblasts.

DNA excision repair was measured in cultured human fibroblasts after single or dual treatments with ultraviolet radiation, 4-nitroquinoline 1-oxide, or N-acetoxy-2-acetylaminofluorene. Three approaches were used to monitor repair: unscheduled DNA synthesis, measured by autoradiography; repair replication, measured by the incorporation of a density-labeled DNA precursor into repaired regions; and excision of ultraviolet endonuclease-sensitive sites. When a single repair- saturating dose of one of the three carcinogens was administered, little stimulation of unscheduled DNA synthesis or repair replication could be observed by additional treatment with one of the other carcinogens. In no instance was total additivity of repair observed. These observations were confirmed by showing that the excision of endonuclease-sensitive sites produced by ultraviolet damage (i.e., pyrimidine dimers) was inhibited by exposure to 4-nitroquinoline 1-oxide and N-acetoxy-2-acetylaminofluorene. The data indicate that the repair of lesions induced by these substances may have common rate-limiting steps, a conclusion previously indicated by the repair deficiency in xeroderma pigmentosum cells in which a single mutation eliminates the repair of damage caused by each of these agents.

4-Nitroquinoline-1-oxide↗
PubMed1978

Postreplication repair of DNA in human fibroblasts after UV irradiation or treatment with metabolites of benzo(a)pyrene.

We have examined the ability of normal fibroblasts and of excision-deficient xeroderma pigmentosum (XP) and XP variant fibroblasts to perform postreplication DNA repair after increasing doses of either ultraviolet (UV) irradiation or mutagenic benzo(a)pyrene derivatives. XP cells defective in the excision of both UV-induced pyrimidine dimers and guanine adducts induced by treatment with the 7,8-diol-9,10-epoxides of benzo(a)pyrene were partially defective in their ability to synthesize high molecular weight DNA after the induction of both classes of DNA lesions. This defect was more marked in XP variant cells, despite their ability to remove by excision repair both pyrimidine dimers and the diol epoxide-induced lesions to the same degree as observed in normal cells. The benzo(a)pyrene 9,10-oxide had no effect in any of the 3 cell lines. The response of the excision and postreplication DNA repair mechanisms operating in human fibroblasts treated with benzo(a)pyrene 7,8-diol-9,10-epoxides, therefore, appears to resemble closely that seen after the induction of pyrimidine dimers by UV irradiation.

Benzopyrenes↗
PubMed1978

Pyrimidine dimer excision in human cells and skin cancer.

We compared three methods for estimating the induction and removal of UV-induced pyrimidine dimers from the DNA of human fibroblasts. Results indicate that after UV doses of 5-20 J/m2, 50% of the dimers are removed by 24 hours. Almost complete excision can be observed if the cells are incubated for periods not less than 72 hours after a dose of 5 J/m2. After higher doses, it probably takes even longer for such complete removal to doses, it probably takes even longer for such complete removal to be seen.

Animals↗
PubMed1977

Partial inhibition of postreplication repair and enhanced frequency of chemical transformation in rat cells infected with leukemia virus.

Postreplication repair of DNA and chemical transformation with the carcinogen 4-nitroquinoline-1-oxide were studied in rat cell lines either uninfected or infected with Rauscher leukemia virus. The results indicate that equivalent amounts of carcinogen are bound to the DNA initially and removed during excision repair. However, the lines differ in that the infected line alone exhibits both sensitivity to nitroquinoline-oxide-induced transformation and a partial inhibition of the postreplication repair process after notroquinoline oxide or UV treatment.

4-Nitroquinoline-1-oxide↗
PubMed1977

Influence of floor surface on the energy cost of wheelchair propulsion.

Carpeting of the type commonly used in hospitals imposed a burden upon normal and patient wheelchair users propelling a wheelchair as reflected in increased energy cost per unit of distance traveled. Wheelchair propulsion also tended to produce high heart rates compared to values reported for normal walking. Pneumatic tires offered no advantage over hard rubber tires on the type of carpet used in this study. Wheelchair propulsion required more energy expenditure per minute than values reported for normal ambulation at the same velocity.

Adult↗
PubMed1976

Effects of nerve stimulation on human muscle.

A phasic program of femoral nerve stimulation was used to reduce refractory knee flexion contractures in five patients. In one, rectus femoris was tenotomized before starting stimulation to reduce hip flexion contracture. Muscle biopsies were performed before and after 5 to 12 weeks of intermittent stimulation at separated sites on the same muscle. In the four patients where muscle contraction was isometric, type I fibers increased 3.7%, 6.4%, 48.4%, anand 30.4%, respectively. Both fiber types in each patient showed an increase in size ( p less than .001). In the tenotomized muscle, where contraction was isotonic at a shortened length, the proportion of type I fibers decreased from 40.2% to 25.4%, and their mean diameter also decreased (p less than .001). These observations suggest that the physical conditions of contraction may be more important than the pattern of neuronal discharge in determining the metabolic profile of human muscle fibers.

Axons↗
PubMed1975

The fate of UV-induced pyrimidine dimers in the nuclear and mitochondrial DNAs of Saccharomyces cerevisiae on various postirradiation treatments and its influence on survival and cytoplasmic "petite" induction.

The photoreactivability of UV-induced pyrimidine dimers in the nuclear and mitochondrial DNAs of Saccharomyces cerevisiae has been investigated in conjunction with the fate of these photoproducts following postirradiation dark incubation in saline and nutrient media. In all instances, survival and "petite" induction were measured. An attempt has been made to relate these results to present ideas on the repair of UV damages in DNA.

Cell Nucleus↗