Potential effects of the herbicide Diuron on mammary and urinary bladder two-stage carcinogenesis in a female Swiss mouse model

Moura, Nelci Antunes de; Grassi, Thiago Luís Magnani; Rodrigues, Maria Aparecida Marchesan; Barbisan, Luı́s Fernando

doi:10.1007/s00204-009-0477-0

Cited by 12 publications

(9 citation statements)

References 31 publications

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“…These changes were related to the influence of high concentrations of Diuron since they have been already reported in our previous studies da Rocha et al;de Moura et al 2010). …”

Section: Histopathologic and Immunohistochemical Analysissupporting

confidence: 75%

Evaluation of Carcinogenic Potential of Diuron in a Rat Mammary Two-Stage Carcinogenesis Model

et al. 2011

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This study aimed to evaluate the carcinogenic potential of the herbicide Diuron in a two-stage rat medium-term mammary carcinogenesis model initiated by 7,12-dimethylbenz(a)anthracene (DMBA). Female seven-week-old Sprague-Dawley (SD) rats were allocated to six groups: groups G1 to G4 received intragastrically (i.g.) a single 50 mg/kg dose of DMBA; groups G5 and G6 received single administration of canola oil (vehicle of DMBA). Groups G1 and G5 received a basal diet, and groups G2, G3, G4, and G6 were fed the basal diet with the addition of Diuron at 250, 1250, 2500, and 2500 ppm, respectively. After twenty-five weeks, the animals were euthanized and mammary tumors were histologically confirmed and quantified. Tumor samples were also processed for immunohistochemical evaluation of the expressions of proliferating cell nuclear antigen (PCNA), cleaved caspase-3, estrogen receptor-a (ER-a), p63, bcl-2, and bak. Diuron treatment did not increase the incidence or multiplicity of mammary tumors (groups G2 to G4 versus Group G1). Also, exposure to Diuron did not alter tumor growth (cell proliferation and apoptosis indexes) or immunoreactivity to ER-a, p63 (myoephitelial marker), or bcl-2 and bak (apoptosis regulatory proteins). These findings indicate that Diuron does not have a promoting potential on mammary carcinogenesis in female SD rats initiated with DMBA.

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“…These changes were related to the influence of high concentrations of Diuron since they have been already reported in our previous studies da Rocha et al;de Moura et al 2010). …”

Section: Histopathologic and Immunohistochemical Analysissupporting

confidence: 75%

Evaluation of Carcinogenic Potential of Diuron in a Rat Mammary Two-Stage Carcinogenesis Model

et al. 2011

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“…once a week from weeks 1 to 5), 1,2‐dimethylhydrazine dihydrochloride [DMH, Tokyo Kasei Industries Co., Japan; four subcutaneous injections (s.c.) of 30 mg kg −1 b.w., twice a week from weeks 3 to 4] and N‐ butyl‐ N‐ (4‐hydroxybutyl)nitrosamine (BBN, Tokyo Kasei Industries Co., Japan; eight doses of 300 mg kg −1 b.w. once a week from weeks 5 to 12; Zapaterini et al ., 2010; de Moura et al ., 2010) plus the gavages of LGEO vehicle (2% Tween 20, five times per week from weeks 14 to 20) LGEO‐treated groups, test groups that received the carcinogens regimen cited above and by gavage LGEO at 125 mg kg −1 or 500 mg kg −1 b.w., respectively (five times per week, from weeks 14 to 20).…”

Section: Methodsmentioning

confidence: 99%

Protective effects of lemongrass (Cymbopogon citratus STAPF) essential oil on DNA damage and carcinogenesis in female Balb/C mice

Bidinotto

Costa

Salvadori

et al. 2010

J of Applied Toxicology

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This study investigated the protective effect of oral treatment with lemongrass (Cymbopogon citratus STAPF) essential oil (LGEO) on leukocyte DNA damage induced by N-methyl-N-nitrosurea (MNU). Also, the anticarcinogenic activity of LGEO was investigated in a multi-organ carcinogenesis bioassay induced by 7,12-dimethylbenz(a)antracene, 1,2-dimethylhydrazine and N-butyl-N-(4-hydroxibuthyl)nitrosamine in Balb/C female Balb/c mice (DDB-initiated mice). In the short-term study, the animals were allocated into three groups: vehicle group (negative control), MNU group (positive control) and LGEO 500 mg kg⁻¹ (five times per week for 5 weeks) plus MNU group (test group). Blood samples were collected to analyze leukocyte DNA damage by comet assay 4 h after each MNU application at the end of weeks 3 and 5. The LGEO 500 mg kg⁻¹ treated group showed significantly lower (P < 0.01) leukocyte DNA damage than its respective positive group exposed to MNU alone at week 3. In the medium-term study, DDB-initiated mice were allocated into three groups: vehicle group (positive control) and LGEO 125 or 500 mg kg⁻¹ (five times per week for 6 weeks; test groups). At week 20, all animals were euthanized and mammary glands, colon and urinary bladder were processed for histopathological analyses for detection of preneoplastic and neoplastic lesions. A slight non-significant effect of treatment with LGEO 500 mg kg⁻¹ in reducing development of alveolar and ductal mammary hyperplasia was found (P = 0.075). Our findings indicate that lemongrass essential oil provided protective action against MNU-induced DNA damage and a potential anticarcinogenic activity against mammary carcinogenesis in DDB-initiated female Balb/C mice.

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“…However, in gliomagenesis, the oncogenic effect is not due to itself since diuron needs to be associated to Akt overexpression to promote the gliomagenesis. The involvement of diuron in carcinogenesis is not new since diuron is already reported for the bladder [14, 15], urothelial [16], skin [17, 18], and mammary [15–19] carcinogenesis. Nevertheless, none of these publications mentioned an impact of diuron on the global level of DNA methylation and on the methylation level of certain gene promoters.…”

Section: Discussionmentioning

confidence: 99%

“…Despite its classification as a likely human carcinogen, little is known about the combination effect of oncogenic overexpression and the pesticide exposure on the glioma occurrence. More generally, little is known about the diuron-induced tumor molecular mechanism even if diuron has been already reported to promote the bladder [14, 15], urothelial [16], skin [17, 18], and mammary [15–19] carcinogenesis.…”

Section: Introductionmentioning

confidence: 99%

Diuron exposure and Akt overexpression promote glioma formation through DNA hypomethylation

et al. 2019

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BackgroundDiuron is an environmental component listed as a likely human carcinogen. Several other studies report that diuron can be oncogenic for bladder, urothelial, skin, and mammary cells. No study mentions the putative effect of diuron on the glioma occurrence.ObjectivesWe here wanted to investigate the effects of diuron exposure on the glioma occurrence while wishing to incriminate a putative implication of DNA methylation modulation in this process.MethodsIn in vivo model of glioma, diuron exposure was firstly compared or combined with oncogenic overexpressions already known to promote gliomagenesis. ELISA quantifying the 5-methylcytosine level on DNA was performed to examine the global DNA methylation level. Quantitative real-time polymerase chain reaction and proximity ligation in situ assay were performed to identify the molecular causes of the diuron-induced changes of DNA methylation. The signatures diuron-induced changes of DNA methylation were analyzed in a cohort of 23 GBM patients.ResultsDiuron exposure is not sufficient to promote glioma, such as the oncogenic overexpression of Akt or Ras. However, the combination of diuron exposure and Akt overexpression promotes glioma. We observed that the diuron/Akt-induced glioma is characterized by three phenotypic signatures characterizing cancer cells: a global DNA hypomethylation, a loss of sensitivity to cell death induction, and a gain of signals of immune escape. Our data associated these phenotypes with three aberrant DNA methylation signatures: the LLT1, PD-L1, and Bcl-w hypomethylations. Strikingly, we observed that these three concomitant hypomethylations were only observed in GBM patients having a potential exposure to diuron via their professional activity.ConclusionsAs single player, diuron is not an oncogenic of glioma, but it can participate to the glioma formation in association with other events (also devoid of oncogenic property as single player) such as Akt overexpression.

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Potential effects of the herbicide Diuron on mammary and urinary bladder two-stage carcinogenesis in a female Swiss mouse model

Cited by 12 publications

References 31 publications

Evaluation of Carcinogenic Potential of Diuron in a Rat Mammary Two-Stage Carcinogenesis Model

Evaluation of Carcinogenic Potential of Diuron in a Rat Mammary Two-Stage Carcinogenesis Model

Protective effects of lemongrass (Cymbopogon citratus STAPF) essential oil on DNA damage and carcinogenesis in female Balb/C mice

Diuron exposure and Akt overexpression promote glioma formation through DNA hypomethylation

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