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Biomedical subjects

Pierre Lebailly

Publications and source records attributed to Pierre Lebailly.

12 recordsLinked to original sources
PubMed2006

Follicular lymphoma-like B cells in healthy individuals: a novel intermediate step in early lymphomagenesis.

Follicular lymphoma is one of the most common adult lymphoma, and remains virtually incurable despite its relatively indolent nature. t(14;18)(q32;q21) translocation, the genetic hallmark and early initiating event of follicular lymphoma (FL) pathogenesis, is also present at low frequency in the peripheral blood of healthy individuals. It has long been assumed that in healthy individuals t(14;18) is carried by circulating quiescent naive B cells, where its oncogenic potential would be restrained. Here, we question this current view and demonstrate that in healthy individuals, t(14;18) is actually carried by an expanding population of atypical B cells issued from germinal centers, displaying genotypic and phenotypic features of FL, and prone to constitute potent premalignant FL niches. These findings strongly impact both on the current understanding of disease progression and on the proper handling of t(14;18) frequency in blood as a potential early biomarker for lymphoma.

B-Lymphocyte Subsets↗
PubMed2006

Mycoflora and multimycotoxin detection in corn silage: experimental study.

Agricultural activities involve the use of crop preservation such as "trench-type" silo, which can sometimes be contaminated by fungi. To investigate the exposure of livestock and farm workers to fungal spores and mycotoxins, a multimycotoxin analysis method has been developed. Six mycotoxins (aflatoxin B1, citrinin, deoxynivalenol, gliotoxin, ochratoxin A, and zearalenone) were quantified by high-performance liquid chromatography coupled to mass spectrometry after solid-phase extraction. An experimental study of fungal species and mycotoxins was conducted in corn silage (Normandy, France) during 9 months of monitoring. The results indicated the recurrence of around 20 different species, with some of them being potentially toxigenic fungi such as Aspergillus fumigatus, Aspergillus parasiticus, Fusarium verticillioides, and Monascus ruber, and the detection of aflatoxin B1 (4-34 ppb), citrinin (4-25 ppb), zearalenone (23-41 ppb), and deoxynivalenol (100-213 ppb). This suggested a possible chronic exposure to low levels of mycotoxins.

Aspergillus↗
PubMed2006

Pesticide contamination of workers in vineyards in France.

In order to build tools to quantify exposure to pesticides of farmers included into epidemiological studies, we performed a field study in Bordeaux vineyards during the 2001 and 2002 treatment seasons to identify parameters related to external contamination of workers. In total, 37 treatment days were observed in tractor operators corresponding to 65 mixing operations, 71 spraying operations and 26 equipment cleaning. In all, four operators with backpack sprayers and seven re-entry workers were also monitored. We performed both detailed observations of treatment characteristics on the whole day and pesticide measurements of external contamination (dermal and inhalation) for each operation. The median dermal contamination was 40.5 mg of active ingredient per day for tractor operators, 68.8 mg for backpack sprayers and 1.3 mg for vineyard workers. Most of the contamination was observed on the hands (49% and 56.2% for mixing and spraying, respectively). The median contribution of respiratory route in the total contamination was 1.1%. A cleaning operation resulted in a 4.20 mg dermal contamination intermediate between a mixing (2.85 mg) and a spraying operation (6.13 mg). Farm owners experienced higher levels than workers and lower contaminations were observed in larger farms. The contamination increased with the number of spraying phases and when equipment cleaning was performed. Types of equipment influenced significantly the daily contamination, whereas personal protective equipment only resulted in a limited decrease of contamination.

Adult↗
PubMed2004

GSTM1, GSTT1, GSTP1 and CYP1A1 genetic polymorphisms and susceptibility to esophageal cancer in a French population: different pattern of squamous cell carcinoma and adenocarcinoma.

AIM: To evaluate the association between CYP1A1 and GSTs genetic polymorphisms and susceptibility to esophageal squamous cell carcinoma (SCC) and esophageal adenocarcinoma (ADC) in a high risk area of northwest of France. METHODS: A case-control study was conducted to investigate the genetic polymorphisms of these enzymes (CYP1A1*2C and GSTP1 exon 7 Val alleles, GSTM1*2/*2 and GSTT1*2/*2 null genotypes). A total of 79 esophageal cancer cases and 130 controls were recruited. RESULTS: GSTM1*2/*2 and CYP1A1*1A/*2C genotype frequencies were higher among squamous cell carcinomas at a level close to statistical significance (OR = 1.83, 95% CI 0.88-3.83, P = 0.11; OR = 3.03, 95% CI 0.93-9.90, P = 0.07, respectively). For GSTP1 polymorphism, no difference was found between controls and cases, whatever their histological status. Lower frequency of GSTT1 deletion was observed in ADC group compared to controls with a statistically significant difference (OR = 13.31, 95% CI 1.66-106.92, P<0.01). CONCLUSION: In SCC, our results are consistent with the strong association of this kind of tumour with tobacco exposure. In ADC, our results suggest 3 distinct hypotheses: (1) activation of exogenous procarcinogens, such as small halogenated compounds by GSTT1; (2) contribution of GSTT1 to the inflammatory response of esophageal mucosa, which is known to be a strong risk factor for ADC, possibly through leukotriene synthesis; (3) higher sensitivity to the inflammatory process associated with intracellular depletion of glutathione.

Acyltransferases↗
PubMed2004

Characterization of the t(14;18) BCL2-IGH translocation in farmers occupationally exposed to pesticides.

Increasing incidence of non-Hodgkin's lymphoma have been associated repeatedly with farming occupation and particular attention focused on the role of pesticide exposure to potentially explain part of this trend. A genetic hallmark of non-Hodgkin's lymphoma is the presence of recurrent chromosomal translocations involving the immunoglobulin heavy chain gene. Of these, the t(14;18), which deregulates BCL2 expression and inhibits apoptosis, is the most frequent in follicular lymphoma and has been detected consistently in peripheral blood lymphocytes of healthy individuals. As BCL2-IGH translocation represents an early step of the malignant process, we evaluated the occurrence and molecular characteristics of BCL2-IGH translocation in 56 individuals occupationally exposed to pesticides in open field farming They were selected from a representative cohort of farmers with a well-defined assessment of pesticide exposure taking into account potential confounding factors, smoking, sunlight, and age. Our results suggest that occupational exposure to pesticides would increase BCL2-IGH prevalence together with the frequency of BCL2-IGH-bearing cells especially during the high pesticide use period. Distribution of BCL2 or IGH breakpoint positions seemed to be independent of pesticide exposure and was similar to those found in other healthy populations or lymphoma patients. Finally, these results provide additional evidence that BCL2-IGH translocation measurements could be a measure of acquired genetic instability in relation to genotoxic exposure in a gene directly relevant in term of lymphomagenesis.

Adolescent↗
PubMed2003

BCL-2/JH translocation in peripheral blood lymphocytes of unexposed individuals: lack of seasonal variations in frequency and molecular features.

BCL-2/J(H) rearrangement has been proposed as a biomarker for evaluating the genotoxicity of occupational and environmental exposures. Available data on time-related modification of this rearrangement in peripheral blood lymphocytes in unexposed healthy individuals is scarce. We investigated the characteristics of BCL-2/J(H) rearrangements in 33 adults unexposed to genotoxins at 2 seasonal time points: winter and spring. BCL-2/J(H) rearrangement was detected in 79% of individuals (detection limit = 8.48 x 10(-8)). Its frequency ranged from <1 to 40 translocations per million lymphocytes with a significant (p = 0.04) positive correlation with age. No significant modifications of BCL-2/J(H) rearrangement frequency or in the number of clones harboring this rearrangement were observed according the 2 time points. No obvious influence of season-related environmental factors on frequency or molecular features of BCL-2/J(H) rearrangements was found in this population suggesting that this would not be a confounding factor.

Adult↗
PubMed2003

Neurodegenerative diseases and exposure to pesticides in the elderly.

The authors investigated the hypothesis that exposure to pesticides could be related to central nervous system disorders in a prospective cohort study of 1,507 French elderly (1992-1998). Lower cognitive performance was observed in subjects who had been occupationally exposed to pesticides. In men, the relative risks of developing Parkinson's disease and Alzheimer's disease for occupational exposure assessed by a job exposure matrix were 5.63 (95% confidence interval: 1.47, 21.58) and 2.39 (95% confidence interval: 1.02, 5.63), respectively, after confounding factors were taken into account. No association was found with having a primary job in agriculture or with environmental pesticide exposure, nor was an association found in women. These results suggest the presence of neurologic impairments in elderly persons who were exposed occupationally to pesticides.

Aged↗
PubMed2002

Urine mutagenicity of farmers occupationally exposed during a 1-day use of chlorothalonil and insecticides.

OBJECTIVES: A study was conducted to evaluate the genotoxic impregnation consecutive to a 1-day open-field spraying of pesticides. METHODS: From 14 farmers (five smokers and nine non-smokers), three urine samples were collected at the end of the spraying season: the morning (S1) of the day of spraying, the evening (S2) and the morning (S3) of the following day. A fourth sample (S0) was obtained before the pesticide-handling period. Mutagenicity of urine extracts was evaluated with the Ames test, using strains TA97a, TA98, TA100 and TA102, with and without S9 mix. RESULTS: The ratio of induced vs spontaneous revertants (induction ratio) was > or =2 in five farmers (including three smokers), with only one strain responding in each. Applying the SALM software proposed by Kim and Margolin in combination with the ANOVA-Dunnett test on crude data (number of revertants), urine extracts were found to be mutagenic on at least one Salmonella strain in 57% and 96% of non-smokers and smokers, respectively. The proportion of mutagenic responses tended to increase from S1 to S3 (not statistically significant) in non-smokers only. Finally, there were no relationships between the relative changes in the number of revertants (adjusted for urine concentration) and any exposure parameters available: area sprayed, number of tanks prepared and time free of exposure to any pesticide. CONCLUSIONS: The lack of significant relationships between urine mutagenicity and exposure data argues against a direct role of the pesticides sprayed, on this impregnation. This result should be considered with caution since the number of farmers involved may limit the significance of the study.

Adult↗
PubMed2002

Biomonitoring of urine mutagenicity with the Ames test: improvement of the extraction/concentration method.

Comparative extraction efficiency of the pre-packed Bakerbond-spe-SDB-1 resin and of Amberlite-AD2 (XAD-2) resin, for the preparation of urine extracts in biomonitoring studies. Urine extracts were prepared in parallel with the Bakerbond column and with the classical XAD-2 resin from urines (1) spiked with mutagenic chemicals, (2) collected from patients after chemotherapy, and (3) from smokers. Mutagenic activities were evaluated on Salmonella typhimurium tester strains TA97a, TA98, TA100 and TA102 with and without S9 mix. Mutagenic activities obtained with Bakerbond extracts were almost always higher or at least equivalent to those prepared on XAD-2 resin. Similar results were observed for the three urine sample groups. When fully validated, the use of the pre-packed columns will be more convenient and time-saving for large population studies.

Antineoplastic Agents↗
PubMed2002

Genetic polymorphisms in microsomal epoxide hydrolase and susceptibility to adult acute myeloid leukaemia with defined cytogenetic abnormalities.

Acute myeloid leukaemia (AML) cases with different chromosomal abnormalities may reflect different aetiologies. Benzene exposure, from a number of sources including smoking, is one risk factor for AML. Individual susceptibility to benzene may depend on differences in expression of metabolizing enzymes. We tested the hypothesis that smoking as well as genetic polymorphisms in the microsomal epoxide hydrolase gene (HYL1), an enzyme involved in benzene metabolism, could be risk factors for AML with defined chromosomal abnormalities. Twenty-six AML cases with -7/del(7q) and 24 cases with t(8;21), as well as 43 cases with normal karyotype and 155 age-, sex- and residence-matched controls, were drawn from a large case-control study on adult acute leukaemia. Current smoking was significantly associated with the cytogenetic abnormalities t(8;21) or -7/del(7q) (OR = 4.9; 95%CI = 2.1-11.5) but not with a normal karyotype, relative to individuals who were not current smokers. A putative high activity HYL1 phenotype [exon 3, residue 113 (Tyr/Tyr) and exon 4, residue 139 (His/Arg or Arg/Arg)] was associated with a significantly increased AML risk in men with -7/del(7q) or t(8;21) (OR = 4.4; 95%CI 1.1-17.0) but not with a normal karyotype. This suggests that AML cases with defined chromosomal abnormalities could be related to specific carcinogen exposures and, furthermore, suggests that smoking and genetic polymorphisms in HYL1 could be risk factors for AML with -7/del(7q) or t(8;21).

Acute Disease↗
PubMedDate not supplied

Association between Parkinson's disease and exposure to pesticides in southwestern France.

A case-control study was performed in southwestern France in order to assess the relationship between pesticide exposure and Parkinson's disease (PD) in the elderly. During the period from 1997 to 1999, 84 cases were recruited together with 252 population-based controls. Experts in occupational health reviewed job codes and provided pesticide exposure levels, making it possible to calculate cumulated exposure lifelong for individuals. Environmental pesticide exposure was considered in relation to the place of residence. A positive association was found with occupational pesticide exposure (odds ratio = 2.2, 95% confidence interval 1.1-4.3) in conditional logistic multiple regression analysis taking into account age, sex, educational level and smoking; however, no clear dose relationship was found. Our results support the hypothesis of an association between occupational pesticide exposure and PD and point to the need to investigate the role of fungicides, for which toxicological hypotheses exist.

Aged↗