A multi-biomarker analysis of DNA damage in automobile painters.

The genotoxic effects associated with automobile painting were analyzed using a panel of biomarkers. Chromosomal aberrations (CAs), sister chromatid exchange (SCE), and micronuclei were evaluated in 25 car painters (12 smokers, 13 nonsmokers) working in different automobile paint-shops in Italy and in 37 control subjects. The controls were healthy blood donors (14 smokers, 23 non-smokers) that were matched with the experimental population for gender and age. Air samples were analyzed regularly at the work places, and elevated concentrations of benzene and toluene were detected consistently. The exposed group had higher frequencies of CAs (both chromosome- and chromatid-type), micronuclei, and SCE (P < 0.5 - P < 0.001). Furthermore, exposed and control subjects were also genotyped for GSTM1 and GSTT1 polymorphism. No significant associations were detected between the biomarker responses and either the GSTM1 or GSTT1 genotype of the subjects, but the small sample size does not allow definite conclusions on the relationship between the genetic polymorphism and the biomarkers. The results indicate that automobile painters have increased levels of clastogenic and possible aneugenic damage and that smoking may be a confounding factor for the responses.

Cytogenetic biomonitoring of workers from laboratories of clinical analyses occupationally exposed to chemicals.

A cytogenetic monitoring study was carried out on a group of workers in clinical analysis laboratories to investigate the risk of occupational exposure to chronic low levels of chemicals.Thirty-four clinical laboratories have been involved in the study. In these laboratories, toxicants and analytical procedures utilized have been characterized. The individual occupational exposure of workers was assessed by use of a questionnaire concerning the chemical substances utilized. About 300 different chemicals have been identified. Cytogenetic analyses (chromosomal aberration and micronucleus tests) were carried out on a strictly selected group of 50 workers enrolled from these laboratories and compared to 53 controls (healthy blood donors) matched for gender and age. The exposed group shows a significantly higher frequency of genetic damage than the control group. Both chromatid and chromosome aberration frequencies in workers appear significantly higher than in controls. Similarly, comparison between micronucleated cells rates of exposed and unexposed groups show significantly higher frequencies of binucleated cells with micronucleus (BNMN) and of total micronuclei (MN tot) in workers than in controls.

Effect of age on DNA binding of the ku protein in irradiated human peripheral blood mononuclear cells (PBMC).

DNA binding of the ku protein was investigated in peripheral blood mononuclear cells (PBMC) from 24 subjects of different ages (20-89 years old) displaying age-related changes in DNA repair, mitotic responsiveness, and cytokine production. Ku is an heterodimeric protein composed of two subunits of 70 and 80 kDa, which is involved in the earliest steps of DNA damage recognition. DNA binding of ku 70/80 was found unchanged in normal PBMC from aging subjects but progressively declined in x-ray-irradiated PBMC from young to adult, and elderly subjects. This finding was concomitant with the age-related fall of DNA repair in the whole population.

Flow cytometric analysis in colorectal carcinoma: prognostic significance of cellular DNA content.

The prognostic value of DNA ploidy status was evaluated prospectively in 70 patients with colorectal carcinoma. Cellular DNA content was measured by flow cytometry from fresh specimens with multiple site sampling. Seventy-five percent of cases exhibited a DNA aneuploid pattern. In a univariate analysis, DNA ploidy status showed a statistically significant correlation with survival (p less than 0.05), weaker than Dukes' stage (p less than 0.001). No correlation was observed between survival and presence of multiple DNA stemlines. In a multivariate analysis, Dukes' stage was the strongest prognostic indicator (p = 0.01) while DNA ploidy status did not show an independent prognostic value. It is concluded that DNA ploidy status is associated with pathological features of aggressive malignancy, but it does not have a determinant role in predicting survival.

Radioimmunotherapy trials in germ testicular carcinoma: a phase I study.

Two patients with germ cell testicular cancer were submitted to radioimmunotherapy (RIT) by using the monoclonal antibody 131I-radiolabelled (MoAb) H17E2, raised against placental alkaline phosphatase (PLAP). Both patients had been previously treated with repeated chemotherapy regimens assisted by autologous bone marrow transplant (ABMT), that, in the end were unsuccessful, thus necessitating further experimental treatment. RIT was well tolerated and the targeting of multiple neoplastic lesions was satisfactory. Nevertheless, the clinical results of treatment were minimal owing to the extension of the tumour. The data obtained suggest the possibility of applying this form of treatment in patients with minimal residual disease after previous traditional chemotherapy regimens.

Pilot study of multiple-fraction daily radiotherapy alternating with chemotherapy in patients with stage IV non-oat cell lung cancer.

From March 1982, 31 patients with stage IV non-oat cell lung cancer have been treated. Radiotherapy was given as three 2.00-Gy fractions on Days 1 and 2, 8 and 9, 22 and 23, and 29 and 30, for a total dose of 48 Gy over a 30-32-day treatment period. A three-drug combination of cyclophosphamide (400 mg/m2), doxorubicin (17 mg/m2), and methotrexate (15 mg/m2) was given on Days 3 and 24 and repeated thereafter every 21 days. Three of 31 evaluable patients (10%) achieved objective complete response and 18 of 31 (58%) achieved partial response (ie, regression of 50%-90%), while no change or disease progression was observed in ten of 31 (32%). The overall response rate in our study was 68%, which is a response much higher than other results in extensive disease. However, controlled trials will be necessary to definitively establish the superiority of this regimen to conventional trials. There was a significant shift of performance status towards higher values after treatment: 12 of the 27 patients classified in the 70-80 Karnofsky category before treatment moved to the higher category, 13 remained in the same status, and only two shifted to the worst category, indicating that the treatment had been effective in giving patients a better quality of life during their survival. The median survival was 35 weeks for the entire group of patients and 44 and 15 weeks for the responders and nonresponders, respectively. One of the primary findings of this pilot study was the ability to give one course of 12 Gy of radiation as multiple fractions per day during each of the first 2 weeks of treatment alternated with one course of chemotherapy, with most patients having very mild or no side effects. Giving multiple daily fractions greater than or equal to 4 hours apart permits the delivery of a large amount of irradiation over a short time period (ie, 1-2 days) within the limits of normal tissue toxicity. Increasing the recovery time of radiotherapy by alternation with chemotherapy offers the possibility of increasing the total radiation dose beyond the upper limits now considered feasible by conventional radiation schedules for induction therapy.(ABSTRACT TRUNCATED AT 400 WORDS)