The aetiology of severe community-acquired pneumonia requiring intensive care unit admission in the Western Cape Province, South Africa.

BACKGROUND: Community-acquired pneumonia (CAP) is a common condition, with mortality increasing in patients who require intensive care unit (ICU) admission. A better understanding of the current aetiology of severe CAP will aid clinicians in requesting appropriate diagnostic tests and initiating appropriate empiric antimicrobials. OBJECTIVES: To assess the comorbidities, aetiology and mortality associated with severe CAP in a tertiary ICU in Cape Town, South Africa. METHODS: We retrospectively analysed a prospective registry of all adults admitted to the medical intensive care unit at Tygerberg Hospital with severe CAP over a 1-year period. RESULTS: We identified 74 patients (mean (SD) age 40.0 (15.5) years; 44 females). The patients had a mean (SD) APACHE II score of 21.4 (7.9), and the mean ICU stay was 6.6 days. Of the 74 patients, 16 (21.6%) died in ICU. Non-survivors had a higher mean (SD) APACHE II score than survivors (28.3 (6.8) v. 19.4 (7.1); p<0.001). Mycobacterium tuberculosis (n=16; 21.6%) was the single most common agent identified, followed by Pseudomonas aeruginosa (n=9; 12.2%). All P. aeruginosa isolates were sensitive to first-line treatment. No organism was identified in 32 patients (43.2%). CONCLUSION: M. tuberculosis was the single most common agent identified in patients presenting with CAP. The mortality of CAP requiring invasive ventilation was relatively low, with a strong association between mortality and a higher APACHE II score.

SOI microdosimetry and modified MKM for evaluation of relative biological effectiveness for a passive proton therapy radiation field.

With more patients receiving external beam radiation therapy with protons, it becomes increasingly important to refine the clinical understanding of the relative biological effectiveness (RBE) for dose delivered during treatment. Treatment planning systems used in clinics typically implement a constant RBE of 1.1 for proton fields irrespective of their highly heterogeneous linear energy transfer (LET). Quality assurance tools that can measure beam characteristics and quantify or be indicative of biological outcomes become necessary in the transition towards more sophisticated RBE weighted treatment planning and for verification of the Monte Carlo and analytical based models they use. In this study the RBE for the CHO-K1 cell line in a passively delivered clinical proton spread out Bragg peak (SOBP) is determined both in vitro and using a silicon-on-insulator (SOI) microdosimetry method paired with the modified microdosimetric kinetic model. The RBE along the central axis of a SOBP with 2 Gy delivered at the middle of the treatment field was found to vary between 1.11-1.98 and the RBE for 10% cell survival between 1.07-1.58 with a 250 kVp x-ray reference radiation and between 1.19-2.34 and 0.95-1.41, respectively, for a Co60 reference. Good agreement was found between RBE values calculated from the SOI-microdosimetry-MKM approach and in vitro. A strong correlation between proton lineal energy and RBE was observed particularly in the distal end and falloff of the SOBP.

MICRODOSIMETRIC MEASUREMENT OF SECONDARY RADIATION IN THE PASSIVE SCATTERED PROTON THERAPY ROOM OF iTHEMBA LABS USING A TISSUE-EQUIVALENT PROPORTIONAL COUNTER.

Measurements of the dose equivalent at different distances from the isocenter of the proton therapy center at iThemba LABS were previously performed with a tissue-equivalent proportional counter (TEPC). These measurements showed that the scattered radiation levels were one or two orders of magnitude higher in comparison to other passive scattering delivery systems. In order to reduce these radiation levels, additional shielding was installed shortly after the measurements were done. Therefore, the aim of this work is to quantify and assess the reduction of the secondary doses delivered in the proton therapy room at iThemba LABS after the installation of the additional shielding. This has been performed by measuring microdosimetric spectra with a TEPC at 11 locations around the isocenter when a clinical modulated beam of 200 MeV proton was impinging onto a water phantom placed at the isocenter.

BRCA1, BRCA2 and PALB2 mutations and CHEK2 c.1100delC in different South African ethnic groups diagnosed with premenopausal and/or triple negative breast cancer.

BACKGROUND: Current knowledge of the aetiology of hereditary breast cancer in the four main South African population groups (black, coloured, Indian and white) is limited. Risk assessments in the black, coloured and Indian population groups are challenging because of restricted information regarding the underlying genetic contributions to inherited breast cancer in these populations. We focused this study on premenopausal patients (diagnosed with breast cancer before the age of 50; n = 78) and triple negative breast cancer (TNBC) patients (n = 30) from the four South African ethnic groups. The aim of this study was to determine the frequency and spectrum of germline mutations in BRCA1, BRCA2 and PALB2 and to evaluate the presence of the CHEK2 c.1100delC allele in these patients. METHODS: In total, 108 South African breast cancer patients underwent mutation screening using a Next-Generation Sequencing (NGS) approach in combination with Multiplex Ligation-dependent Probe Amplification (MLPA) to detect large rearrangements in BRCA1 and BRCA2. RESULTS: In 13 (12 %) patients a deleterious mutation in BRCA1/2 was detected, three of which were novel mutations in black patients. None of the study participants was found to have an unequivocal pathogenic mutation in PALB2. Two (white) patients tested positive for the CHEK2 c.1100delC mutation, however, one of these also carried a deleterious BRCA2 mutation. Additionally, six variants of unknown clinical significance were identified (4 in BRCA2, 2 in PALB2), all in black patients. Within the group of TNBC patients, a higher mutation frequency was obtained (23.3 %; 7/30) than in the group of patients diagnosed before the age of 50 (7.7 %; 6/78). CONCLUSION: This study highlights the importance of evaluating germline mutations in major breast cancer genes in all of the South African population groups. This NGS study shows that mutation analysis is warranted in South African patients with triple negative and/or in premenopausal breast cancer.

Microdosimetry of the Auger electron emitting 123I radionuclide using Geant4-DNA simulations.

Microdosimetric calculations of the Auger electron emitter (123)I were done in liquid water spheres using the Geant4 toolkit. The electron emission spectrum of (123)I produced by Geant4 is presented. Energy deposition and corresponding S-values were calculated to investigate the influence of the sub-cellular localization of the Auger emitter. It was found that S-values calculated by the Geant4 toolkit are generally lower than the values calculated by other Monte Carlo codes for the (123)I radionuclide. The differences in the compared S-values are mainly due to the different particle emission spectra employed by the respective computational codes and emphasizes the influence of the spectra on dosimetry calculations.

Modulation of radiosensitivity in Chinese hamster lung fibroblasts by cisplatin.

The effects of cisplatin exposure time, concentration, and irradiation sequence on the sensitivity of Chinese hamster lung fibroblasts (V79) to gamma-ray exposure were examined. Based on clonogenic cell survival, the cisplatin concentrations corresponding to 50% cell survival (EC(50)) for exposure times of 1 h to 7 days followed a 2-phase exponential decay and ranged from 28.26 +/- 3.32 to 1.53 +/- 0.24 micromol/L, respectively. When cells were treated at EC(50) for exposures of less than 4 h and irradiated immediately, cisplatin inhibited the effect of radiation. Exposures of 4-6 h did not affect radiosensitivity. For exposures of 8-12 h, radiosensitization was observed, which disappeared at 14 h and reappeared for much longer cisplatin treatments. At the lowest achievable EC(50) (1.53 micromol/L), radiosensitization was observed if irradiation was delayed for 1-8 h. This enhancement in radiosensitivity disappeared for irradiation delays of 10-12 h, but reappeared when irradiation was delayed for 14-18 h. These data demonstrate that the mode of interaction between cisplatin and gamma-irradiation depends on the concentration and exposure time of cisplatin, as well as on the timing of irradiation after cisplatin administration. Consideration of changes in cell cycle kinetics may contribute to the improvement of treatment outcomes in adjuvant chemoradiotherapy involving cisplatin.

Toxicity assessment of reference and natural freshwater sediments with the LuminoTox assay.

We examined the possibility of adapting the LuminoTox, a recently-commercialized bioanalytical testing procedure initially developed for aqueous samples, to assess the toxic potential of sediments. This portable fluorescent biosensor uses photosynthetic enzyme complexes (PECs) to rapidly measure photosynthetic efficiency. LuminoTox testing of 14 CRM (Certified Reference Material) sediments was first undertaken with (1) a "solid phase assay" (Lum-SPA) in which PECs are in intimate contact with sediment slurries for a 15 min exposure period and (2) an elutriate assay (Lum-ELU) in which PECs are exposed for 15 min to sediment water elutriates. CRM sediment toxicity data were then compared with those generated with the Microtox Solid Phase Assay (Mic-SPA). A significant correlation (P < 0.05) was shown to exist between Lum-SPA and Mic-SPA, indicating that both tests display a similar toxicity response pattern for CRM sediments having differing contaminant profiles. The sediment elutriate Lum-ELU assay displayed toxicity responses (i.e. measurable IC20s) for eight of the 14 CRM sediments, suggesting that it is capable of determining the presence of sediment contaminants that are readily soluble in an aqueous elutriate. Lum-SPA and Mic-SPA bioassays were further conducted on 12 natural freshwater sediments and their toxicity responses were more weakly, yet significantly, correlated. Finally, Lum-SPA testing undertaken with increasing mixtures of kaolin clay confirmed that its toxicity responses, in a manner similar to those reported for the Mic-SPA assay, are also subject to the influence of grain size. While further studies will be required to more fully understand the relationship between Lum-SPA assay responses and the physicochemical makeup of sediments (e.g., grain size, combined presence of natural and anthropogenic contaminants), these preliminary results suggest that LuminoTox testing could be a useful screen to assess the toxic potential of solid media.

Influence of irinotecan and SN-38 on the irradiation response of WHO3 human oesophageal tumour cells under hypoxic conditions.

Irinotecan and its metabolite SN38 were evaluated for their cytotoxicity and influence on radiosensitivity in WHO3 human oesophageal cells under hypoxic conditions. The IC50's of Irinotecan and SN-38 were found to be 0.8 and 0.04 microM, repectively, with SN-38 emerging as the more potent drug. The toxicities were similar under anoxic conditions. Given in conjunction with irradiation under hypoxic conditions, the two drugs restored the radiosensitivity of WHO3 cells in a dose-dependent manner by factors of 1.5-2.1 as compared to a control oxygen enhancement ratio (OER) of 2.1 in this cell system. In the subtoxic concentration range of 10(-2) microM SN-38 still generated a marked sensitisation of hypoxic tumour cells by factors of 1.2-1.6. It is concluded that the topoisomerase inhibitor Irinotecan and in particular the metabolite SN-38 may be clinically useful for radiotherapy of notoriously hypoxic tumour pathologies.

Proton RBE for early intestinal tolerance in mice after fractionated irradiation.

BACKGROUND AND PURPOSE: To determine the influence of the number of fractions (or the dose per fraction) on the proton relative biological effectiveness (RBE). MATERIALS AND METHODS: Intestinal crypt regeneration in mice was used as the biological endpoint. RBE was determined relative to cobalt-60 gamma rays for irradiations in one, three and ten fractions separated by a time interval of 3.5h. Proton irradiations were performed at the middle of a 7-cm Spread Out Bragg Peak (SOBP). RESULTS: Proton RBEs (and corresponding gamma dose per fraction) at the level of 20 regenerated crypts per circumference were found equal to 1.15+/-0.04 (10.0 Gy), 1.15+/-0.05 (4.8 Gy) and 1.14+/-0.07 (1.7 Gy) for irradiations in one, three and ten fractions, respectively. Alpha/beta ratios as derived from direct analysis of the 'quantal radiation response data' were found to be 7.6 Gy for gamma rays and 8.2 Gy for protons. Additional proton irradiations in ten fractions at the end of the SOBP were found to be more effective than at the middle of the SOBP by a factor of 1.14 (1.05-1.23). CONCLUSION: Proton RBE for crypt regeneration was found to be independent of fractionation up to ten fractions. One can expect that it remains unchanged for higher number of fractions as the lethalities for doses smaller than 3 Gy are exclusively due to direct lethal events. As a tendency for increased effectiveness at the end of the SOBP is reported in the majority of the studies, for clinical applications it would be advisable to allow for by arranging a sloping depth dose curve in the deeper part of the target volume. Finally, it must be noticed that most of in vitro and in vivo RBE values for protons are larger than the current clinical RBE (RBE=1.10).

Comparison of cell inactivation by Auger electrons using the two reagents 4-[123I]iodoantipyrine and [123I]NaI.

The Auger electron emitter 123I was examined in the form of 4-[123I]iodoantipyrine and as [123I]NaI for its effectiveness in killing cells of different sensitivity to photon irradiation. Micronucleus assays showed that 4-[123I]iodoantipyrine is 2-3 times more effective in cell inactivation than [123I]NaI. This can be attributed to the fact that antipyrine, for reason of its lipid solubility, can enter cells and can reach the nucleus, whereas [123I]NaI is excluded from the cytoplasm. In the nucleus Auger decay is conceivably located on the DNA where it may invoke high-LET irradiation damage. Irradiation damage by [123I]NaI is by long range Auger and internal conversion electrons and hence less densely ionising. Results of the present study demonstrate, however, that the enhancement of micronuclei frequency (MNF) seen with 4-[123I]iodoantipyrine as compared to [123I]NaI is similar for all cell lines and that the ratio of 4-[123I]iodoantipyrine/[123I]NaI MN response remains the same. Experiments with the free radical scavenger DMSO, indicated nearly identical dose reduction factors for both 123I carriers. These two observations strongly suggest that the cell inactivation by 4-[123I]iodoantipyrine is not by direct high-LET ionisation of DNA, but is due to an indirect effect. The indirect radiation effect of Auger decay in the nucleus could arise because 4-[123I]iodoantipyrine is not incorporated into the DNA, but is only associated with chromatin where the DNA is shielded by histones.

Recoil proton, alpha particle, and heavy ion impacts on microdosimetry and RBE of fast neutrons: analysis of kerma spectra calculated by Monte Carlo simulation.

Fast neutrons (FN) have a higher radio-biological effectiveness (RBE) compared with photons, however the mechanism of this increase remains a controversial issue. RBE variations are seen among various FN facilities and at the same facility when different tissue depths or thicknesses of hardening filters are used. These variations lead to uncertainties in dose reporting as well as in the comparisons of clinical results. Besides radiobiology and microdosimetry, another powerful method for the characterization of FN beams is the calculation of total proton and heavy ion kerma spectra. FLUKA and MCNP Monte Carlo code were used to simulate these kerma spectra following a set of microdosimetry measurements performed at the National Accelerator Centre. The calculated spectra confirmed major classical statements: RBE increase is linked to both slow energy protons and alpha particles yielded by (n,alpha) reactions on carbon and oxygen nuclei. The slow energy protons are produced by neutrons having an energy between 10 keV and 10 MeV, while the alpha particles are produced by neutrons having an energy between 10 keV and 15 MeV. Looking at the heavy ion kerma from <15 MeV and the proton kerma from neutrons <10 MeV, it is possible to anticipate y* and RBE trends.

Stereotactic proton beam therapy of skull base meningiomas.

PURPOSE: To review outcomes for patients with skull base meningiomas treated using the stereotactic proton beam at the National Accelerator Center (NAC), Republic of South Africa. METHODS AND MATERIALS: Since 1993, 27 patients with intracranial meningiomas have been treated stereotactically with protons at NAC. Of those, 23 were located on the skull base, were large or had complex shapes, and were treated with radical intent. Both stereotactic radiotherapy (SRT, 16 or more fractions) and hypofractionated stereotactic radiotherapy (HSRT, 3 fractions) were used. Eighteen patients underwent proton HSRT, while 5 patients were treated with SRT. The mean target volume for the HSRT group was 15.6 cm(3) (range 2.6-63 cm(3)). The mean ICRU reference dose was 20.3 cobalt Gray equivalent (CGyE), and the mean minimum planning target dose was 16.3 CGyE. The mean clinical and radiologic follow-up periods were 40 and 31 months respectively. The mean volume in the SRT group was 43.7 cm(3), with ICRU reference doses ranging from 54 CGyE in 27 fractions to 61.6 CGyE in 16 fractions. RESULTS: In the HSRT group, 16/18 (89%) of patients remained clinically stable or improved, while 2/18 (11%) deteriorated. Radiologic control was achieved in 88% of patients, while 2 patients had a marginal failure. Among the 5 SRT patients, 2 were clinically better, and 3 remained stable. All SRT patients achieved radiologic control. Three patients (13%), 2 of them in the HSRT group, suffered permanent neurologic deficits. Analyzing different dose/fractionation schedules, an alpha/beta value of 3.7 Gy for meningiomas is estimated. CONCLUSION: Proton irradiation is effective and safe in controlling large and complex-shaped skull base meningiomas.

Monte Carlo simulation of fast neutron spectra: mean lineal energy estimation with an effectiveness function and correlation to RBE.

PURPOSE: Intercomparisons of radiotherapy trials conducted at different fast neutron facilities are complicated by the dependence of the relative biologic effectiveness (RBE) of the different beams on the fast neutrons spectra. To obtain a better understanding of the influence of neutron energy on radiation quality, Monte Carlo simulations were performed to calculate fast neutron (FN) spectra at different irradiation positions. To allow for comparisons with experimental data, the positions were chosen to be the same as that used by other investigators to obtain microdosimetry readings and radiobiological data. METHODS AND MATERIALS: The primary neutron yield for beryllium targets bombarded with protons at the National Accelerator Center, Louvain, Nice, and Orleans facilities were calculated using the FLUKA code. Neutron transport simulations were performed with MCNP-4A, giving FN spectra for various phantom depths, hardening filter thickness, and field sizes. Using an effectiveness function, FN energy groups were correlated with mean lineal energies (y*-values) obtained experimentally by other workers. RESULTS: Calculations confirm earlier measurements that a decrease in beam quality by a hardening filter is the result of a reduction in the low-energy neutron component, i.e., neutrons below 3 MeV. Variations in RBE due to changes in field size and different phantom depths could also be explained by variations of neutrons with energies between 3-15 MeV. The effectiveness function allows one to calculate changes in y* observed for the NAC beam with great accuracy (R(2) = 0.99, p < 0.0001). Also, when this function is applied to beams with different neutron energies, y* calculated values show a very significant correlation with measured RBE values (R(2) = 0.98, p < 0.0001). CONCLUSION: The effectiveness function appears to be suitable to predict changes in y*-values and variations in RBE, using FN spectra simulated for various neutron therapy facilities.

Proton relative biological effectiveness (RBE) for survival in mice after thoracic irradiation with fractionated doses.

PURPOSE: This study aims at providing relative biological effectiveness (RBE) data under reference conditions accounting for the determination of the "clinical RBE" of protons. METHODS AND MATERIALS: RBE (ref. (60)Co gamma-rays) of the 200 MeV clinical proton beam produced at the National Accelerator Centre (South Africa) was determined for lung tolerance assessed by survival after selective irradiation of the thorax in mice. Irradiations were performed in 1, 3, or 10 fractions separated by 12 h. Proton irradiations were performed at the middle of a 7-cm spread out Bragg peak (SOBP). Control gamma irradiations were randomized with proton irradiations and performed simultaneously. A total of 1008 mice was used, of which 96 were assessed for histopathology. RESULTS: RBEs derived from LD50 ratios were found not to vary significantly with fractionation (corresponding dose range, approximately 2-20 Gy). They, however, tend to increase with time and reach (mean of the RBEs for 1, 3 and 10 fractions) 1.00, 1.08, 1.14, and 1.25 for LD50 at 180, 210, 240, and 270 days, respectively (confidence interval approximately 20%). alpha/beta ratios for protons and gamma are very similar and average 2.3 (0.6-4.8) for the different endpoints. Additional irradiations in 10 fractions at the end of the SOBP were found slightly more effective ( approximately 6%) than at the middle of the SOBP. A control experiment for intestinal crypt regeneration in mice was randomized with the lung experiment and yielded an RBE of 1.14 +/- 0.03, i.e., the same value as obtained previously, which vouches for the reliability of the experimental procedure. CONCLUSION: There is no need to raise the clinical RBE of protons in consideration of the late tolerance of healthy tissues in the extent that RBE for lung tolerance was found not to vary with fractionation nor to differ significantly from those of the majority of early- and late-responding tissues.

A comparison of the potential therapeutic gain of p(66)/Be neutrons and d(14)/Be neutrons.

PURPOSE: To determine the relationship between photon sensitivity and neutron sensitivity and between neutron RBE and photon resistance for two neutron modalities (with mean energies of 6 and 29 MeV) using human tumor cell lines spanning a wide range of radiosensitivities, the principal objective being whether or not a neutron advantage can be demonstrated. METHODS AND MATERIALS: Eleven human tumor cell lines with mean photon inactivation doses of 1.65-4. 35 Gy were irradiated with 0-5.0 Gy of p(66)/Be neutrons (mean energy of 29 MeV) at Faure, S.A. and the same plating was irradiated on the same day with 0-10.0 Gy of Cobalt-gamma-rays. Twelve human tumor cell lines, many of which were identical with the above selection, and spanning mean photon inactivation doses of 1.75-4.08 Gy, were irradiated with 0-4 Gy of d(14)/Be neutrons (mean energy of 6 MeV) and with 0-10 Gy of 240 kVp X-rays at the Essen Klinikum. Cell survival was determined by the clonogenic assay, and data were fitted to the linear quadratic equation. RESULTS: 1. Using the mean inactivation dose, a significant correlation was found to exist between neutron sensitivity and photon sensitivity. However, this correlation was more pronounced in the Faure beam (r(2) = 0.89, p

Frequency of radiation-induced micronuclei in neuronal cells does not correlate with clonogenic survival.

It is generally assumed that radiation-induced micronuclei (MN) in cytokinesis-blocked cells are an expression of cellular radiosensitivity. Therefore, radiosensitive cells should have a high frequency of MN and radioresistant cells should show lower levels. We have irradiated cells of a panel of 13 neuronal cell lines of widely differing radiosensitivity [human neuroblastomas: N2alpha, SHSY5Y, SK-N-SH, KELLY and SK-N-BE(2c); murine neuroblastomas: OP-6 and OP-27; human glioblastomas: G120, G60, G28, G112, G44 and G62] and compared their radiation response using the micronucleus and standard clonogenic assays. It was found that micronucleus frequency was much higher in some of the radioresistant cell lines (N2alpha, G28, G120 and G44; SF2 >/= 0.60). These cell lines showed a high frequency of more than 0.32 MN per gray of (60)Co gamma radiation per binucleated cell. On the other hand, the more radiosensitive cell lines (OP-27 and SK-N-SH, SF2

Perceptions of complete dentures by prospective implant patients.

PURPOSE: The purpose of this study was to facilitate the recognition of denture patients who are unable to adapt to conventional dentures and who are likely to benefit from treatment using implant-supported prostheses. MATERIALS AND METHODS: Sixty-nine patients who where referred for postgraduate prosthetic treatment at Wits Dental School completed a self-report inventory of items related to their dentures in current use. Conventional dentures were fabricated for all subjects. Those patients who could not adapt to conventional complete denture treatment were referred for treatment with implant-supported prostheses provided that they conformed with the recommended criteria for this treatment modality. RESULTS: Analysis of the inventory of pretreatment denture complaints yielded variables that differentiated between the group who remained with conventional dentures and the group that was referred for implants. Significant variables were the period that a mandibular denture was used before new dentures were requested (P = 0.025); the period that a maxillary denture was used before further treatment was sought (P = 0.03); the discarding of a mandibular denture (P = 0.035); and pain complaints related to maxillary dentures (P = 0.045). A logistic regression model was used to compare the clinical division of the sample with that determined by the mathematic model. Sixty-six percent of the subjects who accepted conventional treatment and 69% of implant patients corresponded for both classifications. CONCLUSION: The authors conclude that pretreatment denture complaints can be used diagnostic aids for evaluating patients who are likely to benefit from implant-supported prostheses.

Assessment of the micronucleus assay as a biological dosimeter using cytokinesis-blocked lymphocytes from cancer patients receiving fractionated partial body-radiotherapy.

PURPOSE: To assess the suitability of the cytokinesis block micronucleus assay as a biological dosimeter following in-vivo radiation using cancer patients undergoing radiotherapy. METHODS: Blood from 4 healthy donors was irradiated in vitro with gamma-rays and the dose response of induced micronuclei in binucleate lymphocytes following cytokinesis block was determined. Micronucleus frequency was ascertained before and at intervals during radiotherapy treatment in 6 patients with various tumors in the pelvic region. Equivalent whole body doses (physical doses) at these times were calculated from radiation treatment plans and cumulative dose volume histograms. RESULTS: Linear dose response relationships were found for induced micronucleus frequency in lymphocytes resulting from both in-vitro and in-vivo irradiation. Doses resulting from in-vivo irradiation (biological doses) were estimated by substitution of micronucleus frequency observed in radiotherapy patients into the dose response curve from in-vitro irradiation of blood. The relationship between the biologically estimated dose (BD) and the calculated equivalent whole body dose (PD) was BD = 0.868 (+/- 0.043)PD + 0.117 (+/- 0.075). CONCLUSION: The micronucleus assay appears to offer a reliable and consistent method for equivalent whole body radiation dose estimation, although our findings should be confirmed using lymphocytes from radiotherapy patients with tumors at anatomical sites other than the pelvis. Except at doses lower than about ).4 Gy, the method yields dose estimates acceptably close to "true" physically determined doses. The assay can be performed relatively rapidly and can be used as a "first line" biological dosimeter in situations where accidental exposure to relatively high radiation doses has occurred.

The merits of cell kinetic parameters for the assessment of intrinsic cellular radiosensitivity to photon and high linear energy transfer neutron irradiation.

PURPOSE: Differences in tumor response and intrinsic cellular radiosensitivity make the selection of patients for specific radiation modalities very difficult. The reasons for these differences are still unclear, but are thought to be due to genomic and cellular characteristics. Because radiosensitivities vary between cell cycle stages and because S phase cells are very radioresistant, cell cycle kinetic parameters could be a candidate for predicting intrinsic radiosensitivity. METHODS AND MATERIALS: A panel of 15 tumor cell lines was analyzed for S phase content and potential doubling times (Tpot), and the influence of these parameters on the intrinsic radiosensitivity to 60Co gamma- and p(66)/Be neutron irradiation was assessed. RESULTS: S phase content and Tpot show a statistically significant correlation with the mean inactivation dose for photons. The correlation between cell kinetic parameters and the mean inactivation dose for neutrons showed the same trend as photon sensitivity but this was not found to be statistically significant. CONCLUSIONS: S phase content and Tpot were identified as suitable criteria for predicting photon sensitivity. It is suggested that cell kinetic parameters could play a role in identifying neutron sensitive tumors if both tumor and normal cells are analyzed.