New technologies: robotic-assisted laparoscopic dismembered pyeloplasty in adolescents. The first Italian experience.

AIM: The literature about pediatric robotic-assisted laparoscopic dismembered pyeloplasty (RALDP) is poor and limited to few series. This article reports the initial pediatric experience comparing it with the major series. METHODS: Between January 2006 and January 2007 at Umberto Parini Hospital in Aosta three patients were treated for left RALDP by a single senior surgeon. RESULTS: Mean age of the patients was 16.1 years (range 14.9-17.0). Mean body mass index was 21.6 kg/m2 (range 18.7-26.9). All patients were treated for left RALDP. Mean operative time (OT) was 160 minutes (range 120-185). Blood loss was null in all procedures and no interventions were converted to open. Mean postoperative hospitalization was 6.3 days (range 5-8). No intra- or postoperative complications occurred. CONCLUSIONS: This short series demonstrates that RALDP is feasible in adolescents as well and in a peripheral Centre high skilled in adult robotic urology. The OT is excellent in comparison with other series. A preliminary experience in adult robotic surgery and an initial collaboration with urologists for adults are strongly recommended.

Improved therapeutic index of cisplatin by procaine hydrochloride.

The local anesthetic procaine hydrochloride (P.HCl) had little effect on the sensitivity of P388 leukemic cells to cisplatin (DDP) in vitro, but the simultaneous administration of DDP and P.HCl (40 mg/kg) to BDF1 mice produced 50% lethal dose (LD50) and 90% lethal dose (LD90) values approximately two times higher than those observed with DDP alone. DDP-P.HCl diluted in water and administered intraperitoneally (IP) on day 1 and on days 1 and 5 to BDF1 mice bearing P388 leukemic cells produced 33% and 50% cure rates, respectively, at the maximum tolerated dose (16 mg/kg for the single administration and 10 mg/kg given on days 1 and 5). In contrast, under the same conditions, the cure rates obtained with DDP alone (10 mg/kg for the single administration and 8 mg/kg given on days 1 and 5) were 17% and 9%, respectively. Protection from DDP nephrotoxicity seems to be the explanation for the higher doses of DDP that mice can tolerate when DDP is given simultaneously with P.HCl. In fact, the increased blood urea nitrogen (BUN) levels observed 4-7 days following a single IP administration of DDP (8 or 16 mg/kg), as well as the tubular degenerative changes detected by light microscopy, were not observed when the same doses of DDP were given simultaneously with P.HCl. Since DDP nephrotoxicity is known to be reduced when the drug is diluted in 0.9% NaCl solution, we compared the combinations DDP-P.HCl in water, and DDP and DDP-P.HCl in 0.9% NaCl solution. The antitumor activity of DDP diluted in water and administered with P.HCl was similar to that observed in mice treated with DDP alone diluted in 0.9% NaCl solution. However, further improvement of the therapeutic index was achieved after the administration of DDP-P.HCl diluted in 0.9% NaCl solution; this regimen produced a cure rate of 67% (12 of 18 animals). The clinical relevance of these findings is strengthened by the observation that similar results were obtained when P.HCl was given by the intravenous route.

Cefazolin concentrations in serum during cardiopulmonary bypass surgery.

The objective of the study was to investigate possible changes in cefazolin serum levels induced by cardiopulmonary bypass (CPB). Six cardiac male patients who underwent cardiac surgery requiring CPB took part in the study. Cefazolin 2 g was intravenously infused over 60 min before anesthesia and blood samples were taken at appropriate times after drug administration (0, 0.25, 0.5, 1, 4, 6, 8 h), 2 min before and 5 min after the beginning and 2 min before and 5 min after the end of CPB. Drug serum concentrations were determined by means of a microbiological method. Five minutes after the start of CPB, cefazolin serum levels decreased on average by 46.6% and remained steadily low until 5 min after the end of CPB. Then, they rose on average by 37.3% at 4 h and then declined slowly until the last sampling at 8 h. Cefazolin serum concentrations were low during CPB but remained in a potentially effective range for antimicrobial prophylaxis for this surgery.

32P-postlabeling detection of aromatic adducts in the white blood cell DNA of nonsmoking police officers.

Atmosphere in urban areas may be polluted by a number of combustion sources, including industries, vehicle traffic, and residential heating. Traffic police constitute a group of workers that is highly exposed to urban pollutants, especially those from motor vehicle exhaust. We conducted a biomonitoring study to simultaneously measure in 34 nonsmoking police officers and in 36 nonsmoking office workers, as referents, the individual benzo(a)pyrene [B(a)P] exposure using personal samplers and the formation of DNA adducts in peripheral WBCs using 32P-postlabeling techniques. Our results show that the police officers were exposed to significantly higher levels of B(a)P than were referents (P < 0.0001). No seasonal variation of the atmospheric levels of B(a)P was found throughout the year. The median relative adduct labeling x 10(-8) values of the controls and exposed police officers were 0.94 (range, 0.1-3.7) and 1.3 (range, 0.1-5.5), respectively, using the nuclease P1 technique. Although the DNA adduct levels of police officers were globally higher than those of referents (P < 0.05), the difference was entirely due to the summer difference [median values 0.80 (range, 0.1-1.8) and 2.8 (range, 0.7-5.5), respectively (P < 0.001)]. In winter, the DNA adduct levels were substantially identical, and in midseason, there was only a very small increase in police officers, with respect to controls (statistically not significant). Moreover, a more significant seasonal variation of bulky aromatic DNA adduct levels was observed in WBC DNA samples of police officers (P < 0.05) compared to those of referents. The seasonal variation of bulky aromatic adduct levels could be correlated with the reported seasonal variation of aryl hydrocarbon hydroxylase inducibility in human lymphocytes.

(32)P-postlabeling detection of DNA adducts in peripheral white blood cells of greenhouse floriculturists from western Liguria, Italy.

Pesticides are widely used in agriculture to enhance crop yields and to control disease vectors. Floriculturists work frequently in greenhouses and may be exposed to high levels of pesticides, which may result in adverse health effects. To evaluate the relationship between exposure to pesticides and DNA adduct formation in peripheral WBCs of Italian floriculturists, the nuclease P1 modification of a (32)P-postlabeling assay was used to analyze WBC DNA from floriculturists (n = 26) and matched controls (n = 22). DNA adduct-positive samples were more frequent in floriculturists (11/26; 42%) than in matched controls (2/22; 9%) (P < 0.01). Slightly higher frequencies of DNA adduct-positive samples were observed in floriculturists > or = 44 years of age (53%) and in female floriculturists (57%). Floricultural practice was found to be associated with a significantly higher DNA adduct-positive rate in WBCs (rate ratio, 5.12; 95% confidence interval, 1.1-23.7) after allowing for the effects of age and gender. These two latter covariates were not significantly associated with DNA adduct-positive rates. The quantitative levels of DNA adducts were significantly higher in floriculturists than in matched controls according to the Mann-Whitney nonparametric statistic (P = 0.0052). The median adduct level for positive samples among floriculturists was 1.5/10(8) bases. A specific, well-visible spot, named alpha adduct, was detected in 7 out of the 11 DNA adduct-positive samples from floriculturists but in none of the (22 + 20) referent samples (P = 0.0004). The presence of pesticide-related DNA adducts was confirmed clearly using the butanol extraction procedure. Six of 8 floriculturists and 0 of 10 referents were found positive with this method. The median adduct level for positive samples was 6.0/10(8) bases. Two strong spots close to the origin could be identified in all six positive floriculturists, using the butanol extraction procedure. No association between DNA adducts and use of specific pesticides was observed.

Urinary excretion of 1-hydroxypyrene as a marker for exposure to urban air levels of polycyclic aromatic hydrocarbons.

A cross-sectional study was conducted among 94 traffic police officers from the Municipality Police of Genoa, Italy, exposed to airborne pollutants and 52 referent subjects exposed to indoor air pollution levels to investigate the relationships between exposure to ambient air polycyclic aromatic hydrocarbons (PAHs) and urinary excretion of 1-hydroxypyrene (1-OH-P). The effects of smoking, lifestyle factors such as exposure to ETS, and diet, along with the role played by the cytochrome P4501A1 (CYP1A1), and glutathione S-transferase M1 and theta metabolic susceptibility gene polymorphisms were examined. The geometric mean of benzo(a)pyrene air measurements (an index compound of PAH levels) was 70 times higher in traffic police officers (3.67 ng/m3) than in referents (0.05 ng/m3). The urinary concentration of 1-OH-P was clearly associated with cigarette smoking and, to a lesser extent, with exposure to ETS and particulate PAH pollution. No association was detected between 1-OH-P excretion and diet. Women exhibited a higher excretion level than did men, and an apparent effect of age was due to differences in cigarette smoking habits. Exposure to PAHs resulted in higher levels of 1-OH-P excretion in all groups except heavy smokers. Overall, no significant role of any metabolic polymorphism was detected. However, stratification of study subjects according to their smoking habits revealed higher levels of excretion of 1-OH-P in subjects smoking < or =15 cigarettes/day carrying the CYP1A1 polymorphism. No such effect was seen either with nonsmokers or with people smoking more than 15 cigarettes/day. These findings are suggestive of a gene-environment interaction, in which subjects with the CYP1A1 polymorphism, relative to subjects without it, have higher levels of 1-OH-P in their urine at low doses of exposure to PAHs.

Blood levels of reduced and oxidized glutathione in malignant and non-malignant human colorectal lesions.

Glutathione blood levels were determined in colorectal cancer patients (n = 10), patients with adenomatous colorectal polyps (n = 8), and healthy subjects (control group; n = 10). Mean GSH level (micrograms/ml) was significantly higher in cancer patients [515.4 +/- 76.1 (S.D.)] than in those with polyps [407.7 +/- 90.5 (S.D.), P less than 0.05] and the control group [360.9 +/- 67.9 (S.D.), P less than 0.001]. Statistically significant lower GSSG blood level were observed in cancer patients when compared to the other groups. The highest mean blood GSH/GSSG ratio (log transformed) was observed in cancer patients [2.17 +/- 0.108 (S.D.)] and the lowest in healthy subjects [1.88 +/- 0.032 (S.D.)]. All between-group differences in the GSH/GSSG ratio were statistically significant. These findings suggest that glutathione blood levels as well as GSH/GSSG ratio may have applicability as a guide for following the activity of colorectal diseases.

Phase II study of the pure non-steroidal antiandrogen nilutamide in prostatic cancer. Italian Prostatic Cancer Project (PONCAP).

The activity of the pure non-steroidal antiandrogen nilutamide as a single agent was evaluated in 44 patients with metastatic carcinoma of the prostate. Objective (partial) response rates (95% confidence limits) were 38.5 (18.7)% in 26 previously untreated patients and 5.5 (11%) in 18 patients progressing on primary androgen suppressive procedures. The most frequent side-effects were decreased adaptation to darkness (29.5%), slight nausea (31.8%) and alcohol intolerance (18.2%). In addition, treatment was discontinued in 3 patients because of gastrointestinal symptoms. A non-significant increase in testosterone levels was shown in the untreated group during the first month of treatment, after which the levels remained stable. About half of the sexually active men claimed the maintenance of libido and sexual potency during treatment. Although our study confirms a significant incidence of visual disturbances, the activity data coupled with the ability of maintaining sexual interest suggest that single therapy with non-steroidal antiandrogens may deserve comparison to conventional endocrine treatment in controlled trials.

Cisplatin combined with the new cisplatin-procaine complex DPR: in vitro and in vivo studies.

The administration of combinations of platinum compounds is considered as a useful alternative therapeutic strategy to avoid the complications of toxic events during cancer chemotherapy in order to obtain a therapeutic advantage. On the basis of previous in vitro and in vivo findings, suggesting an antitumour activity of the new cisplatin-derived compound cis-diamminechloro-[2-(diethylamino)ethyl 4-amino-benzoate, N4]-chlorideplatinum(II) monohydrochloride monohydrate (DPR), we investigated the effectiveness of the combination of cisplatin (DDP) and DPR in vitro on murine leukaemic cells, which were either sensitive (P388) or resistant (L1210/DDP) to DDP, and on the murine M5076 reticulum cell sarcoma, and in vivo in BDF1 female mice transplanted with P388 leukaemic cells or cisplatin-resistant L1210/DDP leukaemic cells. The contemporaneous exposure in vitro to both platinum compounds gave a significantly higher cell growth inhibition than that expected on the basis of dose-response curves for single agents in all tumour models tested. In vivo, the combinations of DDP plus DPR elicited significant enhancement over the activity of the drugs alone both in the ascitic and solid P388 models. The combined treatment of 10 mg/kg DDP and 14 mg/kg DPR yielded 62.5% tumour-free mice compared with 6.2% with 10 mg/kg DDP alone, the best single agent. It is noteworthy that the combined application of DDP and DPR was also very effective in the solid cisplatin-resistant L1210/DDP model, inducing a significant reduction in the volume of tumour. A therapeutic advantage was achieved with combination treatments that had no effect on platinum-mediated body weight loss and were generally well tolerated by the mice. At equitoxic concentrations of DPR and carboplatin, the treatment with DDP plus DPR proved to have a higher efficacy against this tumour model compared to that observed after the combined treatment with DDP and carboplatin. In summary, the combination of DDP and DPR showed a therapeutic advantage over single drug treatment and has demonstrated promise at the preclinical level in its ability to circumvent acquired resistance to DDP both in vitro and in vivo.

Tumour kinetics, response to chemotherapy and survival in primary ovarian cancer.

The analysis of thymidine labelling index (TLI) in relation to clinico-pathological variables and survival was carried out in 111 ovarian cancer patients. The significance of TLI in predicting response to aggressive first line chemotherapy regimens was examined. The overall median TLI value of 1.8% was used as a cut-off to discriminate slowly from highly proliferating cancers. 94 patients entered into two consecutive randomised trials, and were treated with six courses of cisplatin-based chemotherapy with or without doxorubicin. A significantly higher objective response of 60% was reported in the subset of patients with TLI > 1.8% as compared to 35% in patients with TLI < or = 1.8% (P = 0.03). In addition, patients achieving complete response had tumours with median TLI of 3.8% as compared to 2.4% for partial responders, 1.5% for patients with stable disease and 1.7% for those with progressive disease. A significant increase in tumour kinetics was observed in advanced cancers (P = 0.001), more undifferentiated tumours (P = 0.02) and postsurgical residual disease greater than 2 cm (P = 0.04). In univariate analysis, TLI failed to influence significantly clinical outcome: 26 versus 32 months median survival time for patients with high and low tumour TLI, respectively. In the Cox's regression model, the only independent prognostic variables were performance status and amount of residual disease after primary surgery (P = 0.000).

Prediction of survival by thymidine labelling index in patients with resistant ovarian carcinoma.

The relationship between tumour proliferative activity, evaluated by thymidine labelling index (TLI), clinicopathological variables and clinical outcome, was analysed in a series of 64 chemotherapy-resistant, ovarian cancer patients. The median TLI of 4.6% (range 0.01-45.7) was used as the cut-off to discriminate rapidly from slowly proliferating tumours. Univariate analyses showed a significant advantage in survival for patients with TLI less than or equal to 4.6 (P = 0.0004), ECOG performance status less than or equal to 1 (P = 0.0001) and residual disease after primary surgery less than or equal to 2 cm (P = 0.019). Multivariate analysis demonstrated that performance status was the only independent prognostic variable, although TLI was the last covariate removed from the Cox's regression model.

Regional pharmacokinetic selectivity of intrapleural cisplatin.

The pharmacokinetics and toxicity of cisplatin were investigated in 3 patients affected by malignant mesothelioma who received 90 mg/m2 of the drug intrapleurally. The mean area under the pleural Pt concentration versus time curve (AUC) [12.83 (S.D. 4.06) mg.min/ml] was about 50 times greater than that detected in plasma [0.27 (0.03) mg.min/ml], indicating a clear pharmacological advantage for this route of administration. The mean plasma total Pt concentration was 1.1 micrograms/ml and the apparent total body clearance was 268 (101) ml/min. Platinum plasma pharmacokinetic data measured following intrapleural cisplatin administration (4 patients) were compared with those observed in 7 patients treated intravenously with the same dose of cisplatin (90 mg/m2) under the same modalities of hydration. Intrapleural administration of cisplatin resulted in significantly lower plasma total partial AUC (P less than 0.05) and prolonged plasma levels of filterable Pt compared with intravenous administration. No difference between the two routes of cisplatin administration in the renal clearance (S.D.) of filterable Pt [132 (64) ml/min and 122 (39) ml/min for intravenous and intrapleural cisplatin, respectively] were observed. None of the mesothelioma patients developed clinical symptoms or signs of pleural inflammation. The intrapleural treatment did not produce haemotoxicity and the emetic toxicity was lower compared with that observed in patients receiving cisplatin intravenously.

Heterogeneity of tumor oxygenation: relationship to tumor necrosis, tumor size, and metastasis.

PURPOSE: Measurements of oxygenation in the transplanted rodent KHT-C and SCC-VII tumors demonstrate significant heterogeneity from tumor to tumor as is observed in human tumors. This finding suggests that heterogeneity in oxygenation between tumors is likely related to factors associated with tumor growth rather than to intrinsic genetic differences. In this study we examined whether measurements of the oxygenation of individual KHT-C tumors were related to necrosis in the tumors or to tumor size and whether the more hypoxic tumors gave rise to more metastases. METHODS: Tumors were grown in the gastrocnemius muscle of C3H mice and tumor oxygenation was measured at defined sizes (approx. 0.35 g, 1.0 g, and 2.0 g) using an Eppendorf polarographic oxygen probe. Necrosis was assessed by examining histological sections cut from tumors used for the oxygen measurements. Metastasis was assessed by counting macroscopic lung nodules in mice sacrificed when their tumors reached a size of approximately 2 g. RESULTS: Tumor oxygenation in individual KHT-C tumors became poorer and necrosis became more extensive as the tumors grew larger but, at a size of 0.3-0.4 g, there was no relationship between oxygenation and extent of necrosis. In general, measurements of tumor pO2 at a size of 0.3-0.4 g were predictive of tumor PO2 in the same tumor at a size of about 1 g, but by the time the tumors reached a size of about 2 g they were all very hypoxic. There was a trend suggesting a relationship between macroscopic metastases in the lung and degree of hypoxia in the KHT-C tumors but this was not statistically significant. CONCLUSION: The results indicate that the heterogeneity of oxygenation seen in KHT-C tumors is not explained by different degrees of necrosis in the individual tumors. The lack of a correlation between increased metastasis formation and increased levels of hypoxia in the KHT-C tumors is not consistent with results reported for human tumors.

Protective effect on cisplatin hematotoxicity by procaine hydrochloride.

The ability of procaine hydrochloride (P.HCl) to modulate the effects of cisplatin (DDP) on pluripotent (CFU-S) and committed (CFU-GM) murine hemopoietic stem cells was investigated. DBA/2NCrlBRF1 mice received DDP alone (10 and 16 mg/kg body wt. single i.p. injection) or in combination with P.HCl (40 mg/kg body wt. single i.p. injection). Hemopoietic progenitor cell (HPC) time survival curves were determined up to 14 days following treatment. The simultaneous administration of the lower DDP dose together with P.HCl greatly reduced the hemotoxicity of the antitumoral drug, while this protection was not significant with the higher DDP dose. These results support a role for P.HCl in protecting against DDP hematological toxicity.

Pre-clinical evaluation of new antineoplastic agents in NSCLC cell lines: evidence of histological subtype-dependent cytotoxicity.

The antiproliferative effect of paclitaxel, docetaxel, gemcitabine, topotecan, SN-38 and cis-platin was studied on 5 non-small cell lung cancer (NSCLC) cell lines, 3 of which were adenocarcinoma (ADK) and 2 squamous cell carcinoma (SCC). Cellular chemosensitivity was determined using the MTT in vitro assay after 48, 72 and 96 h of exposure to drug in concentration ranging from 0.001 to 100 microM. A concentration-dependent cell growth inhibition was observed for paclitaxel, gemcitabine, topotecan, SN-38 and cis-platin in all cell lines tested. Docetaxel showed a concentration-independent cytotoxicity and was 104 times more potent than cis-platin (IC50 = 0. 001 vs. 10 microM). Paclitaxel, gemcitabine, topotecan and SN-38 were 102 times more potent than cis-platin, with median IC50 = 0.1 microM at 72 h. The level of drug-induced cell growth inhibition appeared to be correlated, for some of the six drugs tested, with the tumor histological subtype. In particular, topotecan and cis-platin were more active in squamous cell carcinoma than in adenocarcinoma cell lines (p=0.006 and 0.001 respectively at 0.1 microM concentration), while paclitaxel was more active in ADK than in SCC cell lines (p=0.004 at 0.01 microM concentration). Ca-Lu-6, a cell line that, contrary to most other lung cancer cell lines, is wild-type for most oncogenes/tumor suppressor genes, was by far the most sensitive cell line used (p=0.002, 0.003, 0.01 for paclitaxel, topotecan and cis-platin respectively, at 1 microM concentration), showing a >50% growth inhibition to new drugs at a concentration of 0.01 microM. In conclusion, all these new compounds tested were found to be more potent than cis-platin in affecting cellular proliferation of six NSCLC cell lines studied. We suggest that the specific histological subtype and molecular pattern of the cell line being treated could affect the antiproliferative effect of these drugs.

Secondary thyroid carcinoma after allogeneic bone marrow transplantation during childhood.

The aim of this study was to evaluate the incidence and risk factors related to secondary thyroid carcinoma (STC) in patients who have undergone allogeneic BMT during childhood. Data related to the primary hematological disorder and BMT procedure were obtained from the records of 113 patients (42 F; 71 M) who underwent BMT before the age of 18 (median 10.0 years; range 1.7-18.0) and survived more than 3 years after transplant with a median follow-up of 10.1 years (range 3.0-19.0). Sixteen received cranial radiation (CRT) during first-line treatment. Pre-transplant conditioning included TBI in 85 patients, TAI in two, while 26 children did not receive irradiation. The standardized incidence ratio of STC after BMT was significantly higher (P < 0.001) than that of the general population. STC was found in eight patients, 3.1 to 15.7 years after transplant. All received TBI and three also CRT. The Cox's regression analysis, although not statistically significant due to the small study population, showed an increased risk in those who had received a cumulative radiation dose higher than 10 Gy and in those who developed chronic GVHD. Careful follow-up of thyroid status including annual ultrasound examination is recommended for early detection of tumor.

Mortality among shipyard workers in Genoa, Italy.

The dockyards of Genoa are exposed to many known or suspect carcinogenic agents, namely, asbestos, silica, polycyclic aromatic hydrocarbons, and halogenated hydrocarbons; other possibly harmful substances are trace amounts of aromatic amines, welding smokes, paints, and lipid-removing solvents. A cohort study of causes of death of 2190 dockyard workers in Genoa was conducted between January 1, 1960 and December 31, 1975. Mortality rates were calculated for 20 different occupational categories, for which there exist different levels of exposure to noxious substances. Two control groups were selected: the general male population of Genoa and all male employees (462) of San Martino Hospital, Genoa for the same period of time. Causes of death that demonstrated significant excesses for both control groups were: cancer of the colon, excluding the rectum; cancer of the larynx; cancer of the lung, bronchus, and trachea; cancer of the kidney, urinary bladder, and other urinary organs; respiratory diseases; and cirrhosis of the liver. The data obtained from these 20 job categories revealed different types and levels of risk for various carcinogenic agents.

Somatostatin in the management of gastrointestinal fistulas. A multicenter trial.

To evaluate the effectiveness of treatment with total parenteral nutrition (TPN) alone (group A) or combined with continuous intravenous infusion of somatostatin (group B) in postoperative gastrointestinal fistulas, a multicenter, controlled and prospective randomized trial was designed. We present the results obtained after the evaluation of 40 cases (group A, n = 20; group B, n = 20). No significant differences among these treatment schedules were observed in the percentage of closure of fistulas (group A, 81.25%; group B, 85%), but patients treated with total parenteral nutrition plus somatostatin had the fistulas close within a significantly shorter period of time. Moreover, this treatment was associated with a significantly lower morbidity. These preliminary results indicate that somatostatin is a useful therapeutic complement in the conservative treatment of patients with gastrointestinal fistulas.

Sperm antibodies and infertility in patients with testicular cancer.

The level of antisperm antibodies using the enzyme-linked immunosorbent assay (ELISA) in the serum of 48 patients with testicular cancer before and after therapy is reviewed. This is not a linear study of each patient, but some conclusions can be drawn: In a high percentage of testicular cancer patients serum antisperm antibodies can be detected: 73.3 per cent before orchiectomy and 43.7 per cent overall. The percentage of patients with antibodies decreases with adequate therapy. In patients with advanced disease there is a higher percentage of positivity (50%) for serum antisperm antibodies than in patients with low-stage disease (30%). The higher percentage of antibodies-positive patients among those with infertility patterns could be an important argument that supports the hypothesis that autoimmune pathology can play a role in oligo/azoospermia in testicular cancer patients.

Exposure to agrochemicals and DNA adducts in Western Liguria, Italy.

Pesticides are used to control pests and improve agricultural production. Despite their selectivity of action, a number of agrochemicals have been reported to be genotoxic using the (32)P-DNA postlabeling assay. Greenhouse floriculturists are suspected of being heavily exposed to agrochemicals during loading, mixing, and application of pesticides, as well as during manual activities by continuous contact with flowers and ornamental plants. We analyzed the DNA adduct formations in the white blood cells (WBCs) of 57 nonsmoker greenhouse floriculturists and 33 nonsmoker age-matched referents residing in the Western Liguria Region, Italy-the most important Italian greenhouse floriculture area. The averages of DNA adducts, expressed as relative adduct labeling (RAL), were 8.50 x 10(9) +/- 1.98 (SE) in floriculturists and 2.17 x 10(9) +/- 1.05 (SE) in referents. DNA adducts were significantly higher in floriculturists than in controls after adjustment for age and gender (P = 0.007). A specific adduct pattern, with up to six different spots, was observed in 60% of floriculturists, while no adducts were generally detected in controls. Our study represents an important contribution to the correct evaluation of the potential health risk associated with floriculture activity and supports the adoption of measures ensuring pesticide exposure reduction in greenhouses.