RESUMO
PURPOSE: Physical activity (PA) is central to self-management for people with colorectal cancer (CRC) to support health behaviour and function secondary to cancer treatment. However, there is limited evidence on how health professionals (HPs) promote PA during cancer treatment. This study aimed to investigate how and when PA is promoted throughout the chemotherapy pathway among colorectal cancer survivors. METHODS: A qualitative study was conducted with adults with CRC receiving chemotherapy at a large cancer centre. Cross-sectional observation of clinical consultations was conducted at four points during the chemotherapy pathway: prior, midpoint, final cycle, and 8 weeks following chemotherapy. Following completion of treatment, audio-recorded, semi-structured interviews were conducted with patients and HPs and transcribed verbatim. Codes and themes were identified and triangulated from all the data using framework analysis. Observational themes are reported and complimented by interview data. RESULTS: Throughout the chemotherapy pathway (pre, midpoint, end), many opportunities were missed by HPs to promote PA as a beneficial means to maintain functioning and ameliorate cancer treatment side effects. When discussed, PA levels were used only to determine fitness for future oncological treatment. No PA promotion was observed despite patients reporting low PA levels or treatment side effects. Post-treatment, PA promotion was more routinely delivered by HPs, as evidenced by problem-solving and onward referrals to relevant HPs. CONCLUSION: PA promotion was largely absent during treatment despite it being a key component of patient self-management following treatment. This suggests considerable missed opportunities for HPs to provide cancer survivors with PA evidence-based interventions. Further research is necessary to identify how best to ensure PA is promoted throughout the cancer journey. IMPLICATION FOR CANCER SURVIVORS: These findings suggest many may not be receiving support to be physically active during treatment.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Sobreviventes de Câncer/estatística & dados numéricos , Neoplasias Colorretais/terapia , Procedimentos Clínicos , Terapia por Exercício , Exercício Físico/fisiologia , Promoção da Saúde , Idoso , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/reabilitação , Terapia Combinada , Procedimentos Clínicos/organização & administração , Procedimentos Clínicos/normas , Procedimentos Clínicos/estatística & dados numéricos , Estudos Transversais , Terapia por Exercício/organização & administração , Terapia por Exercício/normas , Terapia por Exercício/estatística & dados numéricos , Feminino , Comportamentos Relacionados com a Saúde , Promoção da Saúde/métodos , Promoção da Saúde/organização & administração , Promoção da Saúde/normas , Acessibilidade aos Serviços de Saúde/organização & administração , Acessibilidade aos Serviços de Saúde/normas , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Autocuidado/métodos , Autocuidado/normas , Autocuidado/estatística & dados numéricos , Reino Unido/epidemiologiaRESUMO
BACKGROUND: Radiotherapy can be an effective treatment for prostate cancer, but radiorecurrent tumours do develop. Considering prostate cancer heterogeneity, we hypothesised that primitive stem-like cells may constitute the radiation-resistant fraction. METHODS: Primary cultures were derived from patients undergoing resection for prostate cancer or benign prostatic hyperplasia. After short-term culture, three populations of cells were sorted, reflecting the prostate epithelial hierarchy, namely stem-like cells (SCs, α2ß1integrin(hi)/CD133(+)), transit-amplifying (TA, α2ß1integrin(hi)/CD133(-)) and committed basal (CB, α2ß1integrin(lo)) cells. Radiosensitivity was measured by colony-forming efficiency (CFE) and DNA damage by comet assay and DNA damage foci quantification. Immunofluorescence and flow cytometry were used to measure heterochromatin. The HDAC (histone deacetylase) inhibitor Trichostatin A was used as a radiosensitiser. RESULTS: Stem-like cells had increased CFE post irradiation compared with the more differentiated cells (TA and CB). The SC population sustained fewer lethal double-strand breaks than either TA or CB cells, which correlated with SCs being less proliferative and having increased levels of heterochromatin. Finally, treatment with an HDAC inhibitor sensitised the SCs to radiation. INTERPRETATION: Prostate SCs are more radioresistant than more differentiated cell populations. We suggest that the primitive cells survive radiation therapy and that pre-treatment with HDAC inhibitors may sensitise this resistant fraction.
Assuntos
Inibidores de Histona Desacetilases/farmacologia , Ácidos Hidroxâmicos/farmacologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/patologia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Radiossensibilizantes/farmacologia , Idoso , Idoso de 80 Anos ou mais , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/efeitos da radiação , Ensaio Cometa , Dano ao DNA , Humanos , Masculino , Pessoa de Meia-Idade , Células-Tronco Neoplásicas/efeitos da radiação , Hiperplasia Prostática/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Células Tumorais CultivadasRESUMO
A long-standing prediction of nuclear models is the emergence of a region of long-lived, or even stable, superheavy elements beyond the actinides. These nuclei owe their enhanced stability to closed shells in the structure of both protons and neutrons. However, theoretical approaches to date do not yield consistent predictions of the precise limits of the 'island of stability'; experimental studies are therefore crucial. The bulk of experimental effort so far has been focused on the direct creation of superheavy elements in heavy ion fusion reactions, leading to the production of elements up to proton number Z = 118 (refs 4, 5). Recently, it has become possible to make detailed spectroscopic studies of nuclei beyond fermium (Z = 100), with the aim of understanding the underlying single-particle structure of superheavy elements. Here we report such a study of the nobelium isotope 254No, with 102 protons and 152 neutrons--the heaviest nucleus studied in this manner to date. We find three excited structures, two of which are isomeric (metastable). One of these structures is firmly assigned to a two-proton excitation. These states are highly significant as their location is sensitive to single-particle levels above the gap in shell energies predicted at Z = 114, and thus provide a microscopic benchmark for nuclear models of the superheavy elements.
RESUMO
The defeat of the Aztecs of Mexico by Hernán Cortés in 1521 was but the beginning of a long and torturous conquest of Central America that did not always result in the mastery of people and production for which the Spanish had hoped. The Maya of the resource-poor Yucatán peninsula were spared the heavy colonial hand that held fast to central Mexico and its riches. In addition, the dense forests of the peninsula served as a haven for refugees fleeing oppressive conditions in colonial towns. Despite the paucity of documentary information on Maya communities of the frontier, knowledge of Maya-Spanish relations in the 16th and 17th centuries has advanced in recent years through archeological and ethnohistorical research. Work in one region of the Maya lowlands has brought us closer to an understanding of the early interaction of the rulers and the ruled.
RESUMO
Radiotherapy is still a treatment of choice for many malignancies, often in combination with other strategies. However, its efficacy is limited by the dose that can be safely administered without eliciting serious side-effects, as well as the fact that recurrence is common, particularly in large tumours. Combining radiotherapy with drugs that could sensitise cells to radiation and/or reduce the factors that promote the recovery of the surviving cancer cells is a promising approach. Ionising radiation has been shown to induce senescence and the accumulation of senescent cells creates a microenvironment that facilitates neoplastic growth. This provides a rationale to test the addition of anti-senescent drugs, some of which are already available in the clinic, to radiotherapy protocols. Here, we discuss the relevance of radiotherapy-induced senescent cell accumulation and the potential interventions to minimise its negative effects.
Assuntos
Senescência Celular/efeitos da radiação , Neoplasias/radioterapia , HumanosRESUMO
Mutation induction in directly exposed cells is currently regarded as the main component of the genetic risk of ionizing radiation for humans. However, recent data on the transgenerational increases in mutation rates in the offspring of irradiated parents indicate that the genetic risk could be greater than predicted previously. Here, we have analysed transgenerational changes in mutation rates and DNA damage in the germline and somatic tissues of non-exposed first-generation offspring of irradiated inbred male CBA/Ca and BALB/c mice. Mutation rates at an expanded simple tandem repeat DNA locus and a protein-coding gene (hprt) were significantly elevated in both the germline (sperm) and somatic tissues of all the offspring of irradiated males. The transgenerational changes in mutation rates were attributed to the presence of a persistent subset of endogenous DNA lesions (double- and single-strand breaks), measured by the phosphorylated form of histone H2AX (gamma-H2AX) and alkaline Comet assays. Such remarkable transgenerational destabilization of the F(1) genome may have important implications for cancer aetiology and genetic risk estimates. Our data also provide important clues on the still unknown mechanisms of radiation-induced genomic instability.
Assuntos
Dano ao DNA , DNA/efeitos da radiação , Instabilidade Genômica , Animais , Sequência de Bases , Ensaio Cometa , Primers do DNA , Reparo do DNA , Hipoxantina Fosforribosiltransferase/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos CBA , Mutação , Sequências de Repetição em TandemRESUMO
AIMS: Carbonic anhydrase IX (CA IX) expression has been described as an endogenous marker of hypoxia in solid neoplasms. Furthermore, CA IX expression has been associated with an aggressive phenotype and resistance to radiotherapy. We assessed the prognostic significance of CA IX expression in patients with muscle-invasive bladder cancer treated with radiotherapy. MATERIALS AND METHODS: A standard immunohistochemistry technique was used to show CA IX expression in 110 muscle-invasive bladder tumours treated with radiotherapy. Clinicopathological data were obtained from medical case notes. RESULTS: CA IX immunostaining was detected in 89 ( approximately 81%) patients. Staining was predominantly membranous, with areas of concurrent cytoplasmic and nuclear staining and was abundant in luminal and perinecrotic areas. No significant correlation was shown between the overall CA IX status and the initial response to radiotherapy, 5-year bladder cancer-specific survival or the time to local recurrence. CONCLUSIONS: The distribution of CA IX expression in paraffin-embedded tissue sections seen in this series is consistent with previous studies in bladder cancer, but does not provide significant prognostic information with respect to the response to radiotherapy at 3 months and disease-specific survival after radical radiotherapy.
Assuntos
Antígenos de Neoplasias/metabolismo , Anidrases Carbônicas/metabolismo , Recidiva Local de Neoplasia , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/radioterapia , Idoso , Idoso de 80 Anos ou mais , Anidrase Carbônica IX , Intervalo Livre de Doença , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias da Bexiga Urinária/patologiaRESUMO
It has been proposed that DNA multiply damaged sites (MDS), where more than one moiety in a local region ( approximately 1 helical turn, 10 bp) of the DNA is damaged, are lesions of enhanced biological significance. However, other than indirect measures, there are few analytical techniques that allow direct detection of MDS in DNA. In the present study we demonstrate the potential of protocols incorporating an exonucleolytic snake venom phosphodiesterase (SVPD) digestion stage to permit the direct detection of certain tandem damage, in which two lesions are immediately adjacent to each other on the same DNA strand. A series of prepared oligonucleotides containing either single or pairs of tetrahydrofuran moieties (F), thymine glycol lesions (T(g)) or methylphosphotriester adducts (Me-PTE) were digested with SVPD and the digests examined by either (32)P-end-labelling or electrospray mass spectrometry. The unambiguous observation of SVPD-resistant 'trimer' species in the digests of oligonucleotides containing adjacent F, T(g) and Me-PTE demonstrates that the SVPD digestion strategy is capable of allowing direct detection of certain tandem damage. Furthermore, in studies to determine the specificity of SVPD in dealing with pairs of lesions on the same strand, it was found mandatory to have the two lesions immediately adjacent to each other in order to generate the trimer species; pairs of lesions separated by as few as one or two normal nucleotides behave principally as single lesions towards SVPD.
Assuntos
Dano ao DNA , Diester Fosfórico Hidrolases/química , Timina/análogos & derivados , Alquilação , Cromatografia Líquida de Alta Pressão , Furanos/análise , Oligodesoxirribonucleotídeos/metabolismo , Organofosfatos/análise , Oxirredução , Fosfodiesterase I , Espectrometria de Massas por Ionização por Electrospray , Timina/análiseRESUMO
Tirapazamine (3-amino-1,2,4-benzotriazine-1,4-dioxide, SR 4233) is the lead compound of a new class of hypoxic cell cytotoxins showing considerable antitumor activity. Hypoxic cytotoxicity of tirapazamine is believed to be mediated by free radical attack of its one-electron reduced metabolite on DNA, but little is known about the DNA lesions induced by the drug. Using the anoxic xanthine/xanthine oxidase system to effect one-electron reduction of tirapazamine under controlled conditions, we studied the action of the drug toward pUC18 and calf thymus DNA. Agarose gel electrophoresis indicated that tirapazamine causes substantially higher levels of single-strand breakage than double-stand breakage. The 5' DNA termini at the single-strand breaks were shown to be phosphorylated. Little, if any, base damage was observed when the damaged DNA was analyzed by a 32P-postlabeling assay. The major detectable lesion (comprising approximately 32% of the 3' ends of tirapazamine-induced single-strand breaks) was the phosphoglycolate moiety, which is caused by deoxyribose fragmentation. Since phosphoglycolate formation requires the addition of oxygen, we conclude that tirapazamine acts in a dual fashion to produce phosphoglycolates: (a) to generate a free radical in the deoxyribose ring (i.e., .C-4' and (b) then to donate an oxygen atom. The oxygen donation by tirapazamine was confirmed by anoxic irradiation of DNA in the presence of the unmetabolized drug. Increasing the concentration of the drug (up to 50 microM) led to a dramatic increase in the yield of phosphoglycolate.
Assuntos
Antineoplásicos/farmacologia , Dano ao DNA , DNA/efeitos dos fármacos , Radiossensibilizantes/farmacologia , Triazinas/farmacologia , Glicolatos/metabolismo , TirapazaminaRESUMO
Many genotoxic carcinogens react with the sugar-phosphate backbone in DNA to form phosphotriester (PTE) adducts. These lesions are relatively abundant and persistent for some alkylating carcinogens and may therefore serve as useful biomarkers with which to assess genotoxic exposure and potential mutagenic risk. In the present study, we have developed a 32p postlabeling method that permits analysis of total methyl and/or ethyl PTE in DNA at the femtomole level. The technique is based on the inability of all known nucleolytic enzymes to cleave the internucleotide PTE bond. Consequently, complete digestion of alkylated DNA with these nucleases in the presence of an alkaline phosphatase yields PTE-dinucleoside phosphates. These species are then converted to the corresponding dinucleoside phosphates (dNpdNs) by treatment with alkali to permit subsequent 32p labeling. The resulting labeled dinucleotides (32pd-NpdN) are then analyzed by PAGE. Validation of this method has been carried out using a polydeoxythymidylic acid oligonucleotide containing a site-specific methyl PTE. The method has been applied to the in vitro analysis of calf thymus (CT) DNA treated with dimethylsulfate (DMS) or diethylsulfate (DES) and to the analysis of liver DNA from mice treated in vivo with nitrosodiethylamine. In each case, autoradiograms of the polyacrylamide gels showed the anticipated five bands representing the sixteen labeled dinucleotides, with proportional increases observed as the concentrations of DMS or DES used in the in vitro treatment of CT DNA were increased. The identity and frequency of the nucleosides located 5' to the PTE lesions were obtained by nuclease P1 digestion of the gel-isolated 32pdNpdN species and by analysis of the released labeled mononucleotides, 32pdN, by high-performance liquid chromatography with radioactivity detection. Results obtained from CT DNA treated with DMS or DES showed that the frequency of the four detected nucleotides reflected the normal nucleoside content of CT DNA, indicating the random formation of methyl and ethyl PTE adducts in the in vitro modified DNA. However, studies using liver DNA from three strains of mice treated in vivo with nitrosodiethylamine indicated that the frequency of the thymidine and the 2'-deoxyguanosine 5' to the ethyl PTE was significantly different from the corresponding normal nucleoside content. These results are indicative of (a) the nonrandom formation of ethyl PTE in vivo and/or (b) base sequence-specific ethyl PTE repair.
Assuntos
Adutos de DNA/análise , Dano ao DNA/efeitos dos fármacos , Fosfatos de Dinucleosídeos/análise , Alquilantes , Animais , Carcinógenos/toxicidade , Transformação Celular Neoplásica/induzido quimicamente , Transformação Celular Neoplásica/genética , Marcação por Isótopo , Camundongos , Radioisótopos de FósforoAssuntos
Neoplasias , Radioterapia (Especialidade) , Previsões , Humanos , Neoplasias/radioterapia , RadiobiologiaRESUMO
The risk of recurrence following radiation therapy remains high for a significant number of prostate cancer patients. The development of in vitro isogenic models of radioresistance through exposure to fractionated radiation is an increasingly used approach to investigate the mechanisms of radioresistance in cancer cells and help guide improvements in radiotherapy standards. We treated 22Rv1 prostate cancer cells with fractionated 2 Gy radiation to a cumulative total dose of 60 Gy. This process selected for 22Rv1-cells with increased clonogenic survival following subsequent radiation exposure but increased sensitivity to Docetaxel. This RR-22Rv1 cell line was enriched in S-phase cells, less susceptible to DNA damage, radiation-induced apoptosis and acquired enhanced migration potential, when compared to wild type and aged matched control 22Rv1 cells. The selection of radioresistant cancer cells during fractionated radiation therapy may have implications in the development and administration of future targeted therapy in conjunction with radiation therapy.
Assuntos
Neoplasias da Próstata/genética , Tolerância a Radiação , Fase S , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Docetaxel , Fracionamento da Dose de Radiação , Humanos , Masculino , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Tolerância a Radiação/efeitos dos fármacos , Espécies Reativas de Oxigênio , Fase S/efeitos dos fármacos , Taxoides/farmacologiaRESUMO
Muscle-invasive bladder cancer is a common malignancy with a high mortality rate. Despite ongoing debates about the optimal primary intervention, radical cystectomy remains the cornerstone of first-line therapy in many institutions. Over the past decade, bladder-preserving strategies involving transurethral resection (TUR), chemotherapy and radiotherapy have evolved. However, the advantage of these approaches over radiation treatment as monotherapy has yet to be fully evaluated. In other tumour models, most notably cervical and anal cancer, radiation and chemotherapy delivered concomitantly have resulted in significant survival advantages. Here, we consider the potential value of this approach in the treatment of invasive bladder cancer. Concomitant chemoradiotherapy is currently the mainstay of several bladder-preserving programmes reported in the medical literature. Overall, local control and survival rates compare favourably with contemporary cystectomy series; however, difficulties in drawing valid conclusions are highlighted. Concomitant chemoradiotherapy may have a role in the management of certain patient subgroups, and the debate should remain open. Further large-scale randomised trials are needed, and information regarding bladder function and quality of life after treatment is lacking at present. The importance of close follow-up and prompt salvage cystectomy is emphasised.
Assuntos
Antineoplásicos/administração & dosagem , Radioterapia/métodos , Neoplasias da Bexiga Urinária/terapia , Procedimentos Cirúrgicos Urológicos/métodos , Ensaios Clínicos como Assunto , Terapia Combinada , Humanos , Resultado do Tratamento , Bexiga Urinária/cirurgiaRESUMO
A spectroscopic study of the flavocytochrome b enzyme, cellobiose oxidase, employing optical, NMR, EPR and near infra-red MCD techniques, has identified the axial ligands of the b-type haem. These are a histidine and a methionine, and this ligation set is discussed in relation to the functional role of the haem group.
Assuntos
Desidrogenases de Carboidrato/química , Heme/análise , Dicroísmo Circular , Espectroscopia de Ressonância de Spin Eletrônica , Ligantes , Espectroscopia de Ressonância Magnética , OxirreduçãoRESUMO
The preparation and plasma lipid altering characteristics of a series of 4H-3,1-benzoxazin-4-ones are described. Hypocholesterolemic, hypotriglyceridemic, and high-density-lipoprotein elevating properties are found for derivatives bearing a 4-(1,1-dimethylethyl)phenyl group at the 2-position, and this activity is displayed in both hypercholesterolemic and in normolipidemic rats when the ring system is substituted at position 6 with hydrogen, methyl, chloro, or iodo groups, and is optimal when the 6-position is substituted by a bromine atom. Evidence is presented suggesting that a metabolite or degradation product is responsible for the changes in lipoprotein concentration observed with active molecules of this type. Synthesis of anticipated degradation products of the active molecules gave products displaying the expected in vivo activity, but no improvement in the narrow therapeutic margin of the best compound, 6-bromo-2-[4-(1,1-dimethylethyl)phenyl]-4H-3,1-benzoxazin-4-one, was obtained.
Assuntos
Hipolipemiantes/síntese química , Oxazinas/síntese química , Animais , Fenômenos Químicos , Química , Colesterol/sangue , HDL-Colesterol/sangue , Hipercolesterolemia/tratamento farmacológico , Masculino , Oxazinas/farmacologia , Ratos , Ratos Endogâmicos , Relação Estrutura-Atividade , Triglicerídeos/sangueRESUMO
The effects of postirradiation holding temperature on the yields of radiation-induced single- and double-strand breaks (SSBs and DSBs) in SV40 DNA have been measured by agarose gel electrophoresis. When the DNA is held at low temperatures (< or = 2 degrees C) before and during electrophoresis, the measured yields of radiation-induced SSBs and DSBs are twofold less than in samples exposed to room temperature. In contrast, if the DNA is incubated at 37 degrees C overnight, the yield of DSBs increases twofold over the room temperature assay, while the SSB yield increases only to a small extent (< or = 20%). From a comparison of the various yields, we suggest that low temperature stabilizes radiation-induced labile sites, and that the increased yield of DSBs at 37 degrees C is due either to the recruitment of spatially separate SSBs as DSBs by duplex melting, or to labile sites generating DSBs. The different routes to DSB formation are kinetically distinct. We conclude that room-temperature electrophoresis measures all SSBs including those from labile sites.
Assuntos
DNA de Cadeia Simples/efeitos da radiação , DNA Viral/efeitos da radiação , Vírus 40 dos Símios/genética , Temperatura , Linhagem Celular , Dano ao DNA , Eletroforese em Gel de ÁgarRESUMO
We have measured by gel electrophoresis the yields of single- and double-strand breaks (SSBs and DSBs) induced in aqueous solutions of SV40 DNA and the SV40 minichromosome by 137Cs gamma rays (mean LET 0.3 keV micron-1) and 4He ions (mean LETs 85, 102, and 152 keV microns-1). DNA SSBs are caused mainly by the hydroxyl radicals under these conditions and are reduced in yield as either the hydroxyl radical scavenger concentration or the LET is increased (over the range studied). The G(SSB) for 4He ion irradiation is less by a factor of up to 10 than the G(SSB) for gamma irradiation, depending upon the scavenger concentration. The difference in the yields of SSBs agrees well with the difference in the yields of hydroxyl radicals for the radiations in question. In contrast, the yields of DSBs are similar for gamma and 4He ion irradiation over much of the range of scavenging capacity studied. However, at the highest scavenger concentrations the yields of DSBs are greater for 4He ion irradiation. In addition, the yields of DSBs remain almost constant with increasing LET (over the range studied). Therefore the relative yield of DSBs per SSB increases with increasing LET, supporting the hypothesis that increasing LET leads to an increased clustering of damage in DNA.
Assuntos
Dano ao DNA , DNA de Cadeia Simples/efeitos da radiação , DNA/efeitos da radiação , Dimetil Sulfóxido/farmacologia , Sequestradores de Radicais Livres , Hélio/farmacologia , DNA Viral/efeitos da radiação , Relação Dose-Resposta a Droga , Transferência de Energia , Raios gama , Histonas/efeitos da radiação , Vírus 40 dos Símios/genética , Vírus 40 dos Símios/efeitos da radiaçãoRESUMO
Time-resolved reductions in the light-scattering intensity (LSI) of aqueous oxic and anoxic solutions of poly-C and poly-U at pH 7.8, following pulse-irradiation, have been studied as indices of strand break formation. With doses of 3-24 Gy per pulse, a number of kinetically distinct strand breakage components have been detected. A comparison of the LSI responses obtained from irradiations conducted under N2O with those conducted under air or O2 show no marked difference in the overall extent of LSI change. However, the immediate and fast (t 1/2 less than or equal to 50 microseconds) reduction in LSI, accounting for about 18-19% of the pyrimidine polynucleotide's total LSI response in oxic solution, is reduced in the absence of oxygen, to about 12% of the total LSI response found with poly-C and to about 9% for poly-U. For poly-C there is a five-fold enhancement in the rate of major strand breakage under anoxia [k1(N2O) = 7.9s-1] whereas for poly-U a more modest enhancement (about two-fold) is observed. These enhanced rates are mirrored by those for the losses of the principal optical anoxic absorptions (observed pulse radiolytically) that are assigned to the pyrimidine 6-yl base radicals. Such findings support a proposal that the rate-limiting step of major strand breakage for pyrimidine polynucleotides is a base radical mediated hydrogen atom abstraction reaction (Lemaire et al. 1987, Hildenbrand and Schulte-Frohlinde 1989). Irradiation of poly-C and poly-U in N2O/O2 (4:1, v/v) saturated solutions yields LSI changes much larger than those noted under N2O and air (or O2), which are in turn approximately double the responses observed under N2. This indicates that the major strand breaking species of water radiolysis is the OH-radical and that there is an oxygen enhancement of single strand breakage of about 1.9 for poly-C and 1.6 for poly-U.