Increased Frequency of Micronuclei in Binucleated Lymphocytes among Occupationally Pesticide-exposed Populations: A Metaanalysis

Background: The cytokinesis-block micronucleus (CBMN) assay is a standard cytogenetic tool employed to evaluate chromosomal damage subsequent to pesticide exposure. Objectives: To evaluate the pooled levels of total micronuclei (MN) and binucleated cells with micronuclei (MNC) in 1000 binucleated lymphocytes among population occupationally exposed to pesticides and further determine the more sensitive biomarker of CBMN. Materials and Methods: A meta-analysis on the pooled levels of MN and MNC in binucleated lymphocytes among occupationally pesticide-exposed populations was conducted using STATA 10.0 software and Review Manager 5.0.24 in this study. Results: We found significant differences in frequencies of MN and MNC in 1000 binucleated lymphocytes between pesticide-exposed groups and controls, and the summary estimates of weighted mean difference were 6.82 [95% confidence interval (95% CI): 4.86-8.78] and 5.08 (95% CI: 2.93-7.23), respectively. However, when we conducted sensitivity analyses further, only the MN remained statistically different, but not the MNC, the summary estimates of weight mean difference were 2.86 (95% CI: 2.51-3.21) and 0.50 (95% CI: -0.16-1.17), respectively. We also observed pesticide-exposed subjects had significantly higher MN frequenciesthan controls among smokers and nonsmokers, male and female populations, and American, Asian and European countries in stratified analyses. Conclusions: The frequency of MN in peripheral blood lymphocytes might be a more sensitive indicator of early genetic effects than MNC using the CBMN assay for occupationally pesticideexposed populations.     

Sister chromatid exchange in children of Seventh-Day Adventists and matched controls

The low risk of cancer in Seventh-Day Adventists (SDAs) has been suggested to be due to genetic selection. To investigate this claim we examined the sister chromatid exchange (SCE) frequency in peripheral blood lymphocytes in 16 SDA children in Troms?, all aged 0.5-8 years and 16 controls matched for sex and age. In 12 of 16 pairs, the SDA children had a lower SCE frequency than the controls. The mean difference was 4.06 (95% confidence interval -17.02-8.89, P = 0.51). There was no sex difference, and no correlation between age and SCE frequency. The genetic starting point with regard to SCE frequency seems to be the same for SDA children and controls.     

Breast Cancer Frequency and Exposure to Cadmium: A Meta- Analysis and Systematic Review

Background: In this meta-analysis we review evidence suggesting that exposure to cadmium is a cause ofbreast cancer. Materials and Methods: We conducted Medline/PubMed and Scopus searches using selectedMeSH keywords to identify papers published from January 1, 1980 through January 1, 2013. Data weremerged and summary mean differences were estimated using either a random-effects model or a fixed-effectsmodel. Results: There were 13 studies including 978 exposed cases and 1,279 controls. There was no statisticallysignificant difference in the frequencies of breast cancer between cadmium-exposed and control groups, and thesummary estimate of mean difference was 0.71 (95%CI: 0.33-1.08). However, stratification showed that therewere statistically significant differences in the frequencies of breast cancer between cadmium-exposed and controlgroups among Asian compared with Caucasian population, and the summary estimates of mean difference were1.45 (95%CI: 0.62-2.28) vs. 0.25 (95%CI: -0.09-0.6), respectively. There was a difference in the frequencies ofbreast cancer between cadmium-exposed and control groups in peripheral venous blood sampling methods,and the summary estimate of mean difference was 1.41 (95%CI: 0.46-2.37). Conclusions: Data indicate that thefrequencies of breast cancer might be an indicator of early genetic effects for cadmium-exposed populations.However, our meta-analysis was performed on population-based studies; meta-analysis based on individualdata might provide more precise and reliable results. Therefore, it is necessary to construct an internationaldatabase on genetic damage among populations exposed to cadmium that may contain all raw data of studiesexamining genetic toxicity.     

Sister chromatid exchange induction by diaziquone in human and mouse lymphocytes following both in vivo and in vitro exposures

Diaziquone (AZQ) (NSC 182986), a lipid-soluble benzoquinone derivative currently being tested as an experimental chemotherapeutic agent, was used to treat mouse and human peripheral blood lymphocytes (PBLs) to determine its genotoxic potential by examination of sister chromatid exchange (SCE) induction. In vitro exposure to AZQ caused a linear increase in SCE in both mouse and human PBLs, with mouse PBLs being about twice as sensitive as the human cells. The lowest in vitro concentration found to induce a significant effect on SCE frequency was 0.3 micrograms/ml in mice and 1.0 micrograms/ml in human PBLs. Mice exposed by either i.p. or i.v. injection showed similar dose-related linear increases in SCE frequencies in their PBLs. After i.v. administration of AZQ, splenocytes from treated mice showed approximately the same SCE frequency as found in the PBLs. In general, AZQ caused a slowing of cell cycling in vivo while giving inconsistent responses in vitro. AZQ did cause a dose-related decrease in the number of recoverable mononuclear lymphocytes in mice treated in vivo. Contrary to the in vitro studies, comparison of SCE responses in mice with those previously observed in brain tumor patients undergoing chemotherapy with AZQ (Kligerman et al., Cancer Res., 47: 631-635, 1987) revealed AZQ was a much more potent SCE inducer in humans than in mice.     

Sister chromatid exchange induction in patients with anaplastic gliomas undergoing treatment with radiation plus diaziquone or 1,3-bis(2-chloroethyl)-1-nitrosourea

Diaziquone (AZQ) (NSC 182986), a lipid-soluble benzoquinone derivative, is presently being tested in a Phase III clinical trial to determine its efficacy in patients with anaplastic gliomas compared to the more standard 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) treatment following whole-brain irradiation. These patients on single-drug chemotherapy allowed us to evaluate the effects of each agent on sister chromatid exchange (SCE) induction in vivo. Eight weeks following the final radiation treatment, patients were randomly assigned to one of two groups: (a) 200 mg BCNU/m2, i.v., every 8 weeks; of (b) 15 mg AZQ/m2/day, i.v., for 3 consecutive days, every 4 weeks. Blood (5-10 ml) was drawn by venipuncture before treatment, within 10 h after treatment, and for two BCNU-treated patients at various other times. Peripheral blood lymphocytes were cultured by standard techniques for analysis of SCE. Eight weeks after irradiation but before chemotherapy, the mean SCE frequency in the patients' peripheral blood lymphocytes was 9.6 SCEs/metaphase. Following treatment with AZQ or BCNU, the baseline SCE frequency was increased more than 2-fold or 3-fold, respectively. Two months after BCNU treatment, there was less than a 25% reduction in SCE levels compared to samples taken and cultured within 10 h after treatment. These data show that lesions leading to SCE in human peripheral blood lymphocytes are relatively longlived, and that on a mg/m2 basis, AZQ is a more potent inducer of SCE in vivo than is BCNU.     

Risk Factors for Lung Cancer in the Pakistani Population

Background: Lung cancer is one of the most prevalent malignancies in the world and both incidence andmortality rates are continuing to rise in Pakistan. However, epidemiological studies to identify common lungcancer determinants in the Pakistani population have been limited. Materials and Methods: In this retrospectivecase-control study, 400 cases and 800 controls were enrolled from different hospitals of all provinces ofPakistan. Information about socio-demographic, occupational, lifestyle and dietary variables was extractedby questionnaire from all subjects. Odd ratios (ORs) and 95% confidence intervals (CIs) were calculated. anddose-response associations were also assessed for suitable factors. Results: Strong associations were observed forsmoking (OR=9.4, 95%CI=6.9-12.8), pesticide exposure (OR=5.1, 95%CI=3.1-8.3), exposure to diesel exhaust(OR=3.1, 95%CI=2.1-4.5), red meat consumption (OR=2.9, 95%CI=1.8-4.7) and chicken consumption (OR=2.8,95%CI=1.7-49). Other associated factors observed were welding fumes (OR=2.5, 95%CI=1.0-6.5), sedentaryliving (OR=2.0, 95%CI=1.6-2.6), family history (OR=2.0, 95%CI=0.8-4.9), wood dust (OR=1.9, 95%CI=1.2-3.1), tea consumption (OR=1.8, 95%CI=1.2-2.6), coffee consumption (OR=1.8, 95%CI=1.1-2.8), alcoholism(OR=1.7, 95%CI=1.1-2.5) and asbestos exposure(OR=1.5, 95%CI=0.5-4.4). Consumption of vegetables (OR=0.3,95%CI=0.2-0.4), juices (OR=0.3, 95%CI=0.3-0.4), fruits (OR=0.7, 95%CI=0.5-0.9) and milk (OR=0.6, 95%CI=0.5-0.8) showed reduction in risk of lung cancer. Strongest dose-response relationships were observed for smoking(Χ2=333.8, p≤0.0000001), pesticide exposure (Χ2=50.9, p≤0.0000001) and exposure to diesel exhaust (Χ2=51.8,p≤0.0000001). Conclusions: Smoking, pesticide exposure, diesel exhaust and meat consumption are main lungcancer determinants in Pakistan. Consuming vegetables, fruits, milk and juices can reduce the risk of lung cancerrisk, as in other countries.     

吡虫啉和抑食肼对人体外周血淋巴细胞遗传物质的影响

目的: 研究两种新型杀虫剂-吡虫啉和抑食肼对人体外周血淋巴细胞遗传物质的影响.方法:人体外周血淋巴细胞的微核试验,姐妹染色单体互换试验(SCE)以及单细胞凝胶电泳试验(SCGE,又名彗星试验).结果:在低浓度(吡虫啉为0.05 mg/L,抑食肼为5 mg/L)时,它们对微核和SCE的影响与对照组相比无显著性差异(P>0.05),当浓度升高(吡虫啉为0.1 mg/L,抑食肼为25 mg/L)时,则有显著性差异(P<0.05).而彗星试验在各试验组与对照组相比都有极显著性差异(P<{0.01}),且存在明显的剂量-效应关系(r=0.995, r=0.965).结论:吡虫啉和抑食肼对人外周血淋巴细胞的遗传物质都具有一定程度的损伤作用,相比之下,吡虫啉比抑食肼具有更大的毒性.     

吲哚-3-乙酸对人外周血淋巴细胞微核和SCE频率的影响

背景与目的:研究吲哚-3-乙酸对人体外周血淋巴细胞微核和SCE频率的影响.材料与方法:应用人体外周血淋巴细胞测定吲哚-3-乙酸诱导微核形成率试验和姊妹染色单体互换率(SCE).结果:各吲哚-3-乙酸处理组与阴性对照组相比,微核形成率和SCE差异均存在显著性.结论:吲哚-3-乙酸对人外周血淋巴细胞的遗传物质具有损伤作用.     

Sister chromatid exchange in lymphocytes from renal transplant recipients with and without cancer

The frequency of sister chromatid exchange (SCE) was measured in peripheral blood lymphocytes from control, healthy subjects and immunosuppressed recipients of cadaveric donor kidneys with and without skin cancer. The mean SCE frequency in 43 control subjects was 9.2 per cell (range 5.4-12.3). In 30 transplant recipients with no history or evidence of cancer the mean SCE rate was 10.3 per cell (range 5.8-24.5); four (13%) of these patients had a mean SCE frequency outside the control range. In 7 transplant recipients with skin cancer, the mean SCE frequency was 14.3 per cell (range 9.1-19.9). This was significantly (P less than 0.01) higher than the mean value of control subjects. The mean SCE frequencies in 3 of these 7 patients fell within the control range and in 4 of these patients was above the control range. These results suggest that some immunosuppressed kidney transplant recipients are liable to chromosomal damage.     

Accumulation and persistence of cyclophosphamide-induced sister chromatid exchange in murine peripheral blood lymphocytes

Sister chromatid exchange (SCE) responses were evaluated in lipopolysaccharide-stimulated murine peripheral blood lymphocytes assayed at various times following single or multiple injections of cyclophosphamide (3 mg/kg). Following a single injection, SCE levels in cultured lymphocytes from blood sampled at 5 min, 20 min, 35 min, 1 hr, and 3 hr postexposure were 17.1 +/- 2.0 (S.D.), 19.9 +/- 3.0, 19.3 +/- 1.8, 21.6 +/- 2.4, and 20.6 +/- 2.3, respectively. The control base-line SCE frequency was 11.2 +/- 1.2. The rapid initial increase in SCEs is consistent with the rapid increase reported previously in circulating active metabolites in rats following cyclophosphamide treatment. In peripheral blood lymphocytes cultured at 1 and 24 hr after serial injections of cyclophosphamide (3.0 mg/kg) two, four, and six times (every other day), a dose-related accumulation of SCEs occurred. Accumulation of SCEs was also observed in lymphocytes cultured at 24 and 72 hr following 12 multiple injections (three times weekly) of cyclophosphamide (3 mg/kg) (24.8 +/- 1.5 and 17.6 +/- 1.4, respectively) as compared to the single-injection group assayed at 24 and 72 hr postexposure (16.0 +/- 2.4 and 12.9 +/- 1.4, respectively). In the 12-multiple-injection study, an initial rapid decline at 72 hr was followed by a gradual decrease in SCE levels (1 week, 16.9 +/- 1.3; 2 weeks, 15.2 +/- 0.7; and 4 weeks, 13.4 +/- 1.1) which returned to near base-line (11.2 +/- 0.9) levels at 8 weeks. In the 12-multiple-injection study, successful growth of parallel concanavalin A-stimulated cultures was achieved only at 1, 2, and 4 weeks postexposure. Elevated SCE frequencies were observed at these intervals (16.2 +/- 2.1; 16.7 +/- 0.9; 14.2 +/- 0.3, respectively) relative to base-line SCE levels in concanavalin A-stimulated cells (12.1 +/- 1.8). The observed accumulation of SCEs with repeated exposure and persistence of SCE-inducing lesions parallel human data reported previously. The maximum induced (total minus baseline) SCE levels (10.2) observed in cultured lipopolysaccharide-stimulated lymphocytes from blood sampled at 1 hr after a single 3.0-mg/kg injection of cyclophosphamide were comparable or slightly higher than those (7.1) produced by the same dose of cyclophosphamide in murine bone marrow cells labeled with BrdUrd in vivo. However, in contrast to lymphocytes, bone marrow and alveolar macrophage cells did not accumulate SCEs upon repeated cyclophosphamide treatments.     

Enhancement of benzo[a]pyrene-induced sister chromatid exchanges in lymphocytes from cigarette smokers occupationally exposed to asbestos

The frequencies of base-line and benzo[a]pyrene [(BP) CAS 50-38-8]-induced sister chromatid exchanges (SCE) were measured in peripheral blood lymphocytes from 22 male asbestos-exposed workers and 10 nonexposed workers of comparable age. A clear association between cigarette smoking and asbestos exposure in the sensitivity of lymphocytes to BP was observed. Among asbestos-exposed workers, lymphocytes from those who smoked cigarettes were significantly more susceptible to the induction of SCE by in vitro exposure to BP (P = .01) than were lymphocytes from nonsmokers. Active smoking elevated the base-line SCE frequency in both asbestos-exposed and nonexposed workers (P = .001), and an interaction between smoking and asbestos in the production of base-line SCE was suggested (P = .07). Asbestos exposure alone was not associated with an enhanced susceptibility to the induction of SCE by BP or with an elevation of base-line SCE. Increased age was associated with an increase in SCE inducibility by BP (P = .01), and a history of smoking was marginally associated with SCE inducibility by BP (P = .07). These findings support the hypothesis that an increased susceptibility of asbestos-exposed individuals to polyaromatic hydrocarbon-induced cancer results from an enhanced sensitivity to the induction of genetic damage rather than to an asbestos-induced differential cellular metabolic capacity.     

Sister chromatid exchange induction by benzo(a)pryene in cultured peripheral blood lymphocytes of lung cancer patients and healthy individuals with or without familial history of neoplasms

The inducibility of sister chromatid exchanges (SCEs) by benzo(a)pyrene (BP) was studied in cultured peripheral blood lymphocytes of 15 untreated lung cancer patients and 25 healthy persons including 11 high- and 14 low-cancer-risk individuals tentatively classified by the familial history of lung cancer and other neoplasms. The baseline SCE frequency in cultured lymphocytes was significantly high in lung cancer patients, as compared with all healthy persons or low-cancer-risk individuals. Following exposure to BP, the lymphocytes of lung-cancer patients and high-cancer-risk individuals exhibited significantly greater SCE yields than those of persons at low risk, although no significant difference was observed in the lymphocyte SCE yields when the levels of lung cancer patients were compared with those of all healthy persons. A comparison of the net SCE increase (delta SCE) in BP-exposed lymphocytes among the study groups, however, revealed a significant difference in delta SCE values only between high- and low-cancer-risk individuals. The present findings on both the observed SCE yields and delta SCE values suggest that lymphocytes of high-risk individuals may be more susceptible to BP-induced DNA damage than those of persons at low risk, and that such a chromosomal hypersensitivity to genotoxins may be associated with a high risk of neoplasms.     

The genotoxic effects in lymphocyte cultures of children treated with radiosynovectomy by using yttrium-90 citrate colloid

The aim of this study was to investigate the genotoxic effect on the peripheral blood lymphocytes potentially induced by yttrium-90 citrate colloid (Y-90) in children who were undergoing radiosynovectomy for hemophilic synovitis, using chromosomal aberration analysis (CA) and the micronuclei (MN) assay for detecting chromosomal aberrations, as well as the sister chromatid exchanges (SCE) technique for assessed DNA damage. MATERIALS AND METHODS: Cytogenetic analyses were undertaken in 18 boys (mean age, 14.5 +/- 2.1 years) with hemophilic synovitis who underwent radiosynovectomy with Y-90. CA, MN, and SCE were evaluated just prior to, then at 2 and 90 days following radiosynovectomy from the peripheral lymphocytes of the children. An activity of 185 MBq of Y-90 was injected into the 18 knee joints under aseptic conditions. To check the possibility of leakage from the joint and its migration within the body, the patients underwent scanning under a dual-headed gamma camera at the hours 2 and 48 following the procedure. RESULTS: The procedure was well tolerated in all the children, and there was no extra-articular activity owing to extra-articular leakage of radioactive material in whole-body imaging. The mean frequency of CA in lymphocytes determined prior to the onset of therapy (0.31 +/- 0.48/900 cells) was not significantly increased, in comparison to the control values obtained 2 (0.30 +/- 0.48/900 cells) and 90 days (0.15 +/- 0.37/900 cells) after radiosynovectomy (p = 1.0 and 0.625, respectively). We observed that MN frequency was mildly increased in lymphocytes 2 days after therapy (8.30 +/- 1.89 MN/1000 binucleated cells vs. 9.23 +/- 1.79 MN/1000 binucleated cells; p = 0.013). But there was no significant difference between the baseline and the day 90 control levels of MN (p = 0.196). In the analysis of SCE frequency, there were no significant differences between the baseline (8.11 +/- 0.77) and the control analysis performed 2 and 90 days following radiosynovectomy (8.18 +/- 0.77 and 8.07 +/- 0.74; p = 0.710 and 0.662, respectively). CONCLUSIONS: The results of this study indicated that high radiation doses are not obtained by peripheral lymphocytes of children who undergo Y-90 radiosynovectomy and, therefore, they contradict a high cancer risk.     

Sister chromatid exchanges in lymphocyte cultures of patients previously treated with dibromodulcitol

Acute non-lymphatic leukaemia and myelodysplasia occur in a larger percentage of patients treated with dibromodulcitol (DBD) than in patients treated with other cytostatics. Sister chromatid exchanges (SCE) in the lymphocytes in peripheral blood as well as other haematological parameters were measured in women with breast cancer to investigate whether women who had previously been treated with DBD as a part of their treatment regime had an increased frequency of SCE or another haematological abnormality attributable to DBD. SCE levels were elevated in women treated with DBD as well as in those treated with other cytostatics compared to the untreated control group. All other haematological parameters were normal. There was no significant difference in the number of SCEs between the patients who received DBD and those treated with other cytostatics. The increased frequencies of SCE in the treated patients are attributable to various cytostatic agents, and there is no significant permanent increase in the frequency of SCE after exposure to DBD.     

Sister chromatid exchange in chronic ethylene oxide-exposed primates: unexpected effects of in vitro culture duration, incubation temperature, and serum supplementation

Ethylene oxide (EtO), a potent monofunctional DNA alkylating agent, has been shown to induce sister chromatid exchanges (SCE) in the peripheral blood lymphocytes of animals and workers exposed to it in vivo. We have previously reported that elevations of SCE persist for 6 years after cessation of EtO exposure in cynomolgus monkeys chronically exposed to EtO; the elevation in mean SCE was entirely attributable to a subpopulation of high SCE frequency cells (HFCs). We now report that the detection of persistent HFCs is dependent on the conditions of cell growth, and that EtO exposure increases the replication indices of lymphocytes from the exposed animals when these cells are examined at early cytogenetic harvest times. Culture of lymphocytes in differing serum supplements, changes in cytogenetic harvest times, and alterations in in vitro incubation temperature all markedly affected mean SCE frequency by influencing the detection of HFCs. The frequency of EtO-induced HFCs was independent of 5-bromodeoxyuridine concentration, used for differential staining of sister chromatids. These observations indicate that the detection of persistent alkylation-induced chromosomal changes, observed long after cessation of in vivo chronic exposure of these animals, is highly dependent upon factors affecting cell growth.     

Biological monitoring of fire fighters: sister chromatid exchange and polycyclic aromatic hydrocarbon-DNA adducts in peripheral blood cells

Fire fighters are exposed to potentially carcinogenic combustion and pyrolysis products during the course of their work. The present study was designed to test 43 fire fighters and matched controls for DNA damage which might be related to occupational carcinogen exposures. Using peripheral blood lymphocytes, we examined (a) baseline sister chromatid exchange (SCE) frequency and (b) SCE induction by in vitro mutagenic challenge with mitomycin C. Using nucleated peripheral blood cells, we examined (c) polycyclic aromatic hydrocarbon-DNA adduct levels by assessing benzo(a)pyrene diol epoxide (BPDE)-DNA antigenicity. Exposures were determined from histories of fire-fighting activity. The presence of confounding factors (e.g., tobacco smoking, charcoal-broiled food consumption, etc.) was determined by questionnaire. Plasma cotinine levels were measured to assess recent exposures to tobacco smoke. White fire fighters exhibited a significantly higher risk for the presence of detectable BPDE-DNA antigenicity than white controls (odds ratio, 3.4; 95% confidence interval, 1.08-10.5 after adjustment). Consumption of charcoal-broiled food less than 3 times a month was associated with a smaller proportion of individuals exhibiting measurable (positive) BPDE-DNA antigenicity, while consumption of broiled food greater than 3 times a month did not affect the proportion of positive individuals. Daily alcohol consumption was associated with a larger proportion of individuals exhibiting positive BPDE-DNA antigenicity, (P = 0.07). Tobacco smoking and charcoal-broiled food consumption, but not fire fighting, were associated with increased levels of baseline SCE. Sensitivity to SCE induced by mitomycin C in cultured peripheral lymphocytes was similar in fire fighter and control groups. However, sensitivity of individual fire fighters to mitomycin C-induced SCE was correlated with number of fires fought in the previous 24 h.     

Persistently elevated sister chromatid exchanges in ethylene oxide-exposed primates: the role of a subpopulation of high frequency cells

Ethylene oxide (EtO) is a potent DNA-alkylating agent which has been shown to induce sister chromatid exchanges (SCE) in the peripheral blood lymphocytes of exposed workers. To study further the persistence of EtO-induced SCE, we have examined lymphocytes from a group of cynomolgus monkeys exposed to EtO in control, 50-ppm, and 100-ppm concentrations for 7 h/day, 5 days/week over the years 1979-1981. The data collected in 1987 were compared with those generated immediately prior to the cessation of exposure in 1981. EtO-induced SCE persisted at levels significantly above those of the nonexposed controls. Comparison of the distributions of SCE between 1979 and 1987 shows that, although mean SCE decreased from 1981 to 1987, the mean SCE in the top 10% of the distribution has not diminished over time. Consequently, the increased level of SCE is entirely attributable to a subpopulation of cells with high frequencies of SCE. These findings suggest that long-lived lymphocytes may inefficiently repair EtO-induced lesions which produce SCE. The results also have important implications for the proper use of SCE analytical techniques in the epidemiological study of cytogenetic damage after chronic exposure to DNA-alkylating agents.     

Cancer incidence among pesticide applicators exposed to metolachlor in the Agricultural Health Study

Metolachlor is one of the most widely used herbicides in the United States. We evaluated the incidence of cancer among pesticide applicators exposed to metolachlor in the Agricultural Health Study, a prospective cohort study of licensed pesticide applicators in Iowa and North Carolina. A total of 50,193 pesticide applicators were included. Detailed information on pesticide exposure and lifestyle factors was obtained from self-administered enrollment questionnaires completed between 1993 and 1997; average length of follow-up was 7.33 years. Two metolachlor exposure metrics were used : (i) lifetime days personally mixed or applied metolachlor and (ii) intensity-weighted lifetime days (lifetime days x an intensity level). Poisson regression analysis was used to estimate relative risks (RR) and 95% confidence intervals (95%CI) for cancer subtypes by tertiles of metolachlor exposure. No clear risk for any cancer subtype was found for exposure to metolachlor. A significantly decreased RR was found for prostate cancer in the highest category of lifetime days exposure (RR = 0.59; 95%CI, 0.39-0.89) and in the second highest category of intensity-weighted lifetime days exposure (RR = 0.66; 95%CI, 0.45-0.97); however, the test for trend was not significant for either exposure metric. A nonsignificantly increased risk was found for lung cancer with lifetime days exposure in the highest category (RR = 2.37; 95%CI, 0.97-5.82, p-trend = 0.03) but not with intensity-weighted lifetime days. Given the widespread use of metolachlor and the frequent detection of metolachlor in both surface and ground water, future analyses of the AHS will allow further examination of long-term health effects, including lung cancer and the less common cancers.     

Novel responses of peripheral lymphocytes of cancer patients to chemical induction of sister chromatid exchanges

Sensitivities to sister chromatid exchange (SCE) induction by chemicals of peripheral lymphocytes from 26 cancer patients were estimated under conditions identical to those for healthy humans which had been reported (Cancer Res., 43: 439-442, 1983). The sensitive individual was defined as one whose cells give a mean induced SCE frequency more than 2 standard deviation units above the population mean of induced SCEs in cells from the healthy humans. When cells were treated with 3-amino-1-methyl-5H-pyrido[4, 3-b]indole in the presence of rat liver S9 mix, 8 in 10 stomach cancer patients, 4 in 4 colon cancer patients, 3 in 9 lung cancer patients, 0 in 3 patients bearing other cancers, and 0 in 9 non-cancerous individuals were sensitive. The corresponding frequency of individuals in the healthy population, reported previously, was 1 in 33 persons. Thus, the frequency of sensitive individuals in the combined group of stomach and colon cancer patients was very significantly higher than were frequencies in control groups. Three in 10 patients with stomach cancer and 4 in 16 patients with other cancers were sensitive to induction of SCE by methyl methanesulfonate. Six in these 7 methyl methanesulfonate-sensitive patients were also 3-amino-1-methyl-5H-pyrido[4,3-b]indole sensitive. The frequency of methyl methanesulfonate-sensitive individuals in the healthy populations was 2 in 50. There was no patient who was sensitive to SCE induction by 4-nitroquinoline 1-oxide. The frequency was not significantly different from the healthy population, in which 3 in 50 persons were sensitive. These results suggest that a particular cancer correlates with the sensitivity of peripheral lymphocytes to SCE induction by particular chemicals.