maneb and Skin-Neoplasms

The objective of the study was to examine the association between occupational exposure to pesticides and cutaneous melanoma, controlling for all possible confounders.. A pooled analysis of two case-control studies was conducted in two different geographic areas (Italy and Brazil). Detailed pesticides exposure histories were obtained.. Ever use of any pesticide was associated with a high risk of cutaneous melanoma (odds ratio 2.58; 95% confidence interval 1.18-5.65) in particular exposure to herbicides (glyphosate) and fungicides (mancozeb, maneb), after controlling for confounding factors. When subjects were exposed to both pesticides and occupational sun exposure, the risk increased even more (odds ratio 4.68; 95% confidence interval 1.29-17.0).. The study suggests an augmented risk of cutaneous melanoma among subjects with exposure to pesticides, in particular among those exposed to occupational sun exposure.

Topics: Adult; Aged; Brazil; Case-Control Studies; Female; Fungicides, Industrial; Glycine; Glyphosate; Herbicides; Humans; Italy; Male; Maneb; Melanoma; Middle Aged; Occupational Diseases; Occupational Exposure; Odds Ratio; Pesticides; Risk Factors; Skin Neoplasms; Sunlight; Surveys and Questionnaires; Young Adult; Zineb

Mancozeb, ethylene(bis)dithiocarbamate fungicides, has been well documented in the literature as a multipotent carcinogen, but the underlying mechanism remains unrevealed. Thus, mancozeb has been selected in this study with the objective to decipher the molecular mechanism that culminates in carcinogenesis. We employed two-dimensional gel electrophoresis and mass spectrometry to generate a comparative proteome profile of control and mancozeb (200 mg/kg body weight) exposed mouse skin. Although many differentially expressed proteins were found, among them, two significantly upregulated proteins, namely, S100A6 (Calcyclin) and S100A9 (Calgranulin-B), are known markers of keratinocyte differentiation and proliferation, which suggested their role in mancozeb-induced neoplastic alterations. Therefore, we verified these alterations in the human system by using HaCaT cells as an in vitro model for human skin keratinocyte carcinogenesis. Upregulation of these two proteins upon mancozeb (0.5 μg/mL) exposure in HaCaT cells indicated its neoplastic potential in human skin also. This potential was confirmed by increase in number of colonies in colony formation and anchorage-independent growth assays. Modulation of S100A6/S100A9 targets, elevated phosphorylation of extracellular signal regulated kinase (ERK1/2), Elk1, nuclear factor- kappa B and cell division cycle 25 C phosphatase, and cyclin D1 and cyclooxygenase-2 upregulation was seen. In addition, PD98059 (ERK1/2 inhibitor) reduced cell proliferation induced by mancozeb, confirming the involvement of ERK1/2 signaling. Conclusively, we herein present the first report asserting that the mechanism involving S100A6 and S100A9 regulated ERK1/2 signaling underlies the mancozeb-induced neoplastic potential in human skin.

Topics: Animals; Blotting, Western; Calgranulin B; Cell Cycle; Cell Cycle Proteins; Cell Line, Tumor; Cell Proliferation; Cell Transformation, Neoplastic; Fungicides, Industrial; Humans; Keratinocytes; Male; Maneb; Mice; Phosphorylation; S100 Calcium Binding Protein A6; S100 Proteins; Signal Transduction; Skin; Skin Neoplasms; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Zineb

We evaluated the effects of mancozeb (Dithane M4-5), a protective carbamate fungicide, on transplacental carcinogenesis in Swiss albino mice. Mancozeb, a polymeric complex of ethylene bis (dithiocarbamate) manganese with zinc salt, is reported to possess carcinogenic and cocarcinogenic activity in various tumor models. In the present study, pregnant Swiss albino mice were administered mancozeb intraperitoneally on the 14th day of gestation. The first filial generation (F1 progeny) was promoted with a well-known tumor promoter 12-o-tetradecanoyl phorbol-13-acetate (TPA). The results revealed a significantly high tumor incidence (72%) in the F1 progeny of the animals initiated with mancozeb or a well known carcinogen 7,12-dimethyl benzanthracene (DMBA) and promoted with TPA in comparison to animals that were either from mothers given only the vehicle (DMSO) and promoted with TPA in F1 progeny or not promoted with TPA in F1 progeny. No significantly higher tumor incidence was observed in any other experimental groups. These results suggest that mancozeb or its metabolites are capable of crossing the placental barrier and can exert DNA damage and tumor initiating consequences in the fetal cells that, after promotion with TPA, get converted into neoplastic cells.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinogens; Disease Models, Animal; Female; Fungicides, Industrial; Male; Maneb; Maternal Exposure; Maternal-Fetal Exchange; Mice; Pregnancy; Prenatal Exposure Delayed Effects; Skin Neoplasms; Tetradecanoylphorbol Acetate; Zineb

The effect of mancozeb, a fungicide, on mouse skin ornithine decarboxylase (ODC) activity and DNA synthesis was studied. ODC activity was induced after topical application of mancozeb and exhibited a peak level at 5 h. This ODC induction was dependent on the dose of mancozeb applied. Cycloheximide, an inhibitor of protein synthesis, inhibited the mancozeb-caused ODC induction, indicating the effect on enzyme protein synthesis. The rate of DNA synthesis was also increased by mancozeb, as indicated by increased [3H]thymidine incorporation into skin DNA. Induction of ODC activity and DNA synthesis are among the events probably involved in the tumorigenic action of mancozeb on mouse skin.

Topics: Animals; Cycloheximide; DNA; Female; Fungicides, Industrial; Maneb; Mice; Ornithine Decarboxylase; Skin; Skin Neoplasms; Tetradecanoylphorbol Acetate; Zineb

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Cocarcinogenesis; Female; Fungicides, Industrial; Maneb; Mice; Skin Neoplasms; Thiocarbamates; Zineb

Mancozeb, a polymeric complex of ethylene bis (dithiocarbamate) manganese with zinc salt is a protective fungicide. In the present study complete carcinogenic activity of mancozeb, has been observed following topical application on dorsal mouse skin. Female Swiss albino mice were exposed to mancozeb at a dose of 100 mg/kg body weight dissolved in 100 microliters dimethyl sulfoxide 3 times per week. Development of tumours was observed after 31 weeks (217 days) of mancozeb application. A high rate of mortality was observed after 54 weeks (378 days) of mancozeb application due to its toxicity and the study was terminated after 60 weeks. On histological examination, these tumours were found mostly to be benign in nature, e.g., squamous cell papillomas and keratoacanthomas.

Topics: Administration, Topical; Animals; Body Weight; Fungicides, Industrial; Maneb; Mice; Papilloma; Skin Neoplasms; Survival Analysis; Zineb

In this study the tumour-promoting activity of a carbamate fungicide, mancozeb, has been observed following topical application on mouse skin in a two-stage initiation--promotion protocol for carcinogenesis. Female Swiss albino mice were initiated with a single subcarcinogenic dose (52 micrograms) of 7,12-dimethylbenz[a]anthracene painted on the interscapular region. Seven days after initiation the mice underwent topical application of mancozeb (100 mg/kg body wt) three times per week as promoter. Development of tumours was observed after 12 weeks of mancozeb application in 1/14 animals and 100% tumorigenesis was recorded after 17 weeks of mancozeb application. On histological examination, these tumours were found mostly to be benign in nature, e.g. squamous cell papillomas and keratocanthomas.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Cocarcinogenesis; Female; Fungicides, Industrial; Maneb; Mice; Skin Neoplasms; Thiocarbamates; Zineb

Mancozeb is a protectant fungicide and is a polymeric complex of ethylene bis(dithiocarbamate)manganese (i.e. Maneb) with zinc salt. In this study, the tumour initiating ability of mancozeb has been observed by a 2-stage initiation-promotion protocol in mouse skin.

Topics: Animals; Carcinogens; Female; Maneb; Mice; Papilloma; Skin; Skin Neoplasms; Tetradecanoylphorbol Acetate; Thiocarbamates; Zineb