Protective effect of lycopene against radiation-induced hepatic toxicity in rats.

The radioprotective effect of lycopene against liver damage was investigated in 80 female Sprague Dawley rats (10 per group). Early-group rats included: controls (group 1), lycopene (group 2), radiotherapy alone (group 3), and lycopene + radiotherapy (group 4). Lycopene (5 mg/kg per day) was administered orally for 7 days; single-fraction 8 Gy abdominopelvic radiotherapy was administered on day 8. Early-group rats were sacrificed on day 10. Late-group rats (groups 5-8) underwent treatment with the same regimens but, in groups 6 and 8, lycopene was administered until all rats were sacrificed, 60 days postradiotherapy. Liver malondialdehyde levels increased significantly and glutathione (GSH) levels, GSH-peroxidase (GSH-Px) and superoxide dismutase (SOD) activity decreased significantly in radiotherapy versus control groups. In lycopene + radiotherapy groups, malondialdehyde levels decreased significantly and GSH levels, GSH-Px and SOD activity increased significantly compared with radiotherapy groups. No significant between-group histo pathological differences were observed in early groups; in late groups, histopathological changes increased significantly in the radiotherapy group versus control group. A significant decrease in histopathological changes occurred in the lycopene + radiotherapy group compared with the radiotherapy group. Lycopene supplementation significantly reduced radiotherapy-induced oxidative liver injury.

Multiple primary malignant neoplasms from the black sea region of Turkey.

Long-term cancer survival is increasing and, as a consequence, so is the prevalence of secondary malignancies. This study evaluated the patient and tumour characteristics of 117 patients with multiple primary malignant neoplasms (MPMN). The incidence of MPMN in children and adults was 0.28% and 1.23%, respectively. The male : female ratio was 1.7 : 1. The mean ± SE age at tumour diagnosis was 60.56 ± 1.18 years. Overall, the top three tumour sites were the larynx, bladder and breast. Among secondary tumours, lung cancer was the most frequent, followed by breast and colon cancer. Among males, the leading primary and secondary tumour sites were the larynx (30.1%) and lung (50.7%), respectively. Among females, the breasts were both the leading primary (32.6%) and secondary (37.2%) cancer site. The mean ± SE overall survival was 97.2 ± 15.0 months. During follow-up, the brain was the most commonly observed site of metastasis. The occurrence and characteristics of MPMN reported in the literature are also reviewed. The present study contributes towards increasing understanding and treatment of MPMN in a different population group.

The effect of pre-operative conventional and hyperfractionated radiotherapy schedules on wound healing and tensile strength in rats: an experimental study.

We examined the effects of pre-operative conventional and hyperfractionated radiotherapy schedules on wound healing and tensile strength in 90 female Wistar rats weighing between 182 and 240 g. The animals were randomized into three groups (n = 30 each). Group I was sham-irradiated. Group II (conventional) received 20 daily fractions of 200 cGy, to a total dose of 4000 cGy. Group III (hyperfractionated) received 40 fractions of 120 cGy, twice daily, to a total dose of 4800 cGy. Four weeks after radiotherapy, incision and primary repair with simple suturing was performed on one side of the neck. Twenty-one days after wounding, all the rats were sacrificed. Non-parametric Kruskal-Wallis and Mann-Whitney U-tests were used for the statistical analysis of wound tensile strength. The chi-squared test was used for the statistical analysis of the histopathologic findings. The hyperfractionated group had a significantly lower tensile strength than that of the control group (P = 0.03, z = -2.18). According to the histopathologic findings, fibrosis was increased significantly in the hyperfractionated group as compared to the other groups (P = 0.038, chi2 = 6.52). Hyperfractionated radiotherapy significantly reduced the wound tensile strength in the early evaluation period as compared to the control group.

Prognostic significance of seizure in patients with glioblastoma multiforme.

BACKGROUND: Several prognostic factors have been described but there are few studies evaluating the prognostic importance of seizure in patients with glioblastoma multiforme (GBM). AIMS: To evaluate the prognostic importance of seizure at the time of the diagnosis of glioblastoma multiforme (GBM) and compare it with other known prognostic factors. SETTINGS AND DESIGN: Between January 1994 and December 2000, 81 patients underwent irradiation for intracranial GBM at our institution. The criteria for inclusion in this study were biopsy-proven GBM, being treated for primary disease. Seventy-six patients were retrospectively evaluated and the remaining five patients could not be enrolled due to lack of details. MATERIAL AND METHODS: The prognostic importance of age, sex, performance status, a history of seizure at diagnosis, extent of surgery, radiotherapy field and dose were studied. STATISTICAL ANALYSIS: The Kaplan-Meier method, the Log rank test, the Cox proportional hazard model and the Mann-Whitney U test were used for statistical analysis. RESULTS: Survival at first and second years was 19.74% and 4.81%, respectively. Univariate analysis revealed age, performance status, history of seizure, and radiotherapy dose as significant prognostic factors and with multivariate analysis age, history of seizure and radiotherapy dose were positive prognostic factors. CONCLUSION: This study concluded that in GBM, history of seizure prior to diagnosis of GBM was a positive prognostic factor.

The frequency of illegitimate TCRbeta/gamma gene recombination in human lymphocytes: influence of age, environmental exposure and cytostatic treatment, and correlation with frequencies of t(14;18) and hprt mutation.

Chromosome translocations in lymphoid malignancies often involve V(D)J recombinase mediated events giving rise to aberrant T-cell receptor (TCR) and immunoglobulin genes, which have been suggested to be useful as markers of genomic instability, genotoxic exposure and cancer risk. Illegitimate rearrangements involving the TCRbeta/gamma loci on chromosome 7 create TCRbeta/gamma hybrid genes which occur at low frequency in peripheral blood lymphocytes (PBLs) of normal healthy individuals. To evaluate the utility of this marker, we studied the possible effects of age and genotoxic exposures on the TCRbeta/gamma gene variant frequency (VF), and compared the frequencies of hypoxanthine guanine phosphoribosyl transferase (hprt) mutation, hprt exon 2/3 deletion, t(14;18) and TCRbeta/gamma gene rearrangements in cells from the same donors. The TCRbeta/gamma VF ranged five-fold among 16 middle aged blood donors with a mean of 0.74+/-0.29/10(5) PBLs, which is consistent with our previous estimate in healthy subjects. The TCRbeta/gamma VF was found to increase from birth until early adult life, and then to decrease with increasing age. Four testis cancer patients, who 6 years earlier had been treated with etoposide and other cytostatic drugs, showed TCRbeta/gamma VF similar to that in healthy controls. No increase of the TCRbeta/gamma VF was found among non-smoking PAH-exposed aluminum smelter workers compared to non-smoking controls. Smoking smelter workers showed decreased TCRbeta/gamma VF compared to non-smoking workers and controls, but in a follow-up study 2 years later the difference was no longer statistically significant, although the smoking smelter workers still showed a lower TCRbeta/gamma VF than the controls. No correlation was obtained between the TCRbeta/gamma VF and the t(14;18) or hprt mutant frequency (MF) in a group of healthy individuals. However, there was a statistically significant correlation between the TCRbeta/gamma VF and the hprt exon 2/3 deletion frequency in PBL DNA from the same donors. These results show that the TCRbeta/gamma VF in healthy individuals changes with age and correlates with the frequency of hprt exon 2/3 deletion, another marker of aberrant V(D)J recombination in T-cells. However, no effect of smoking or present or previous exposure to genotoxic agents on TCRbeta/gamma VF was observed in this study. Thus, further studies are needed to prove the utility of TCRbeta/gamma gene rearrangement as a marker of genotoxic exposure.

Variations in the frequency of T-cell receptor beta/gamma-interlocus recombination in long-term cultures of non-irradiated and X- and gamma-irradiated human lymphocytes.

PURPOSE: The increased level of illegitimate V(D)J recombination at the T-cell receptor (TCR) loci in lymphoid tumours as well as in T lymphocytes of ataxia telangiectasia patients and humans exposed to carcinogens in vivo suggest that site-specific interlocus recombination events could serve as markers of genomic instability and early genetic changes associated with carcinogenesis. The purpose of this study was to investigate the ability of ionizing radiation to induce TCRbeta/gamma-interlocus rearrangements in human lymphocytes in vitro. MATERIALS AND METHODS: Peripheral blood lymphocytes (PBL) from two healthy donors were exposed to 3 Gy of either X- or gamma-irradiation in vitro. Growth factor-stimulated cell cultures were established, and cell samples for DNA extraction were taken immediately after exposure and at several time points during long-term growth. A PCR-based method was used to measure the frequency of variant cells with Vgamma-Jbeta1 TCR rearrangements. RESULTS: The frequency of TCRbeta/gamma-variant cells was not significantly different in the irradiated and control cultures at any time studied up to 55 days after PHA-stimulation, indicatin that V(D)J-mediated Vgamma-Jbeta1 rearrangement is not induced by X- or gamma-irradiation under these conditions. However, in both irradiated and non-irradiated cultures, the frequency of TCRbeta/gamma variants increased approximately fourfold after mitogen stimulation, from a normal background level of 0.3-0.4 x 10(-5) to 1.3-1.6 x 10(-5) at days 4-9. These levels then gradually declined during prolonged cultivation, and after 2-4 weeks the frequency of variant cells was below the detection limit ( < 0.13 x 10(-5)). CONCLUSIONS: These results provide no evidence that TCRbeta/gamma gene rearrangements can be induced by X- or gamma-irradiation in vitro. However, in contrast with cells with normal TCR receptors, TCRbeta/gamma-variant cells display a relative growth advantage for 1-2 weeks, followed by gradual loss of proliferative capacity. Eventually, they are eliminated from the cell population or outnumbered by cells with normal TCR. If there are similar differences in vivo between cells with hybrid and normal TCR, this may explain the previously reported time- and season-dependent changes in the frequency of cells with hybrid TCR in occupationally exposed populations and individuals receiving cytostatic treatment.

Frequency and cell specificity of T-cell receptor interlocus recombination in human cells.

Immunoglobulin and T-cell receptor (TCR) genes are assembled by a site-specific rearrangement known as V(D)J [variable-(diversity)-joining] recombination. These rearrangements occur normally in pre-B- and pre-T-cells using signal sequences adjacent to coding exons for immunoglobulin and TCR genes, respectively. However, aberrant recombination may result in the generation of hybrid TCR genes by joining of TCR-beta with TCR-gamma specific sequences. Such hybrid TCR genes occur at a low frequency in peripheral blood lymphocytes (PBL) of healthy individuals, and can be detected by PCR amplification. We have determined the in vivo frequency of hybrid V gamma-J beta 1 TCR (hybrid TCR) genes in lymphocyte DNA from 12 healthy individuals. The average frequency was found to be 5.83 in 0.75 x 10(6) PBL, with a threefold difference between the highest and lowest individual value. The presence of similar TCR gene rearrangements in individual samples suggests that T-cells with a hybrid TCR gene are capable of clonal expansion in vivo. The individual hybrid TCR gene frequency remained relatively constant during 72 hours of in vitro cultivation. In long-term culture, the frequency gradually decreased, and after 28 days no hybrid TCR genes were detectable in lymphocyte DNA. These results show that T-cells with a hybrid TCR gene are able to respond to mitogen stimulation in vitro, and may have a proliferative disadvantage or are selected against during prolonged in vitro cultivation. No hybrid TCR genes were detected in ten proliferating T-cell clones, indicating that the rate of hybrid TCR gene formation is < 2.0 x 10(-8) per cell per cell division. No hybrid TCR genes were detected in DNA from B-lymphocytes, sperm, granulocytes, fibroblasts, keratinocytes, and three B-lymphoblastoid ataxia telangiectasia cell lines. In agreement with previous reports, the frequency of hybrid TCR genes in peripheral blood DNA from two ataxia telangiectasia patients was found to be more than 15-fold higher than in lymphocytes from normal individuals. These data show that formation of hybrid TCR genes is restricted to T-cells in vivo, and occurs at a very low frequency, if at all, in proliferating T-cells in vitro, and with an increased frequency in patients with ataxia telangiectasia.