Disease relevance of Neocidol

• PURPOSE: We tested the hypothesis that organochlorines are a risk factor for breast cancer, using prospectively gathered data on serum levels of DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene] (the main metabolite of the pesticide DDT [2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane]) and polychlorinated biphenyls (PCBs) [1].
• Dichlorodiphenyltrichloroethane (DDT) is a compound with moderate toxicity that is judged to be safe for occupational use, although little is known about its long-term effects on the human nervous system [2].
• FINDINGS: Serum concentrations of p,p'-DDT were significantly higher in pancreatic cancer cases with a K-ras mutation than in cases without a mutation (odds ratio for upper tertile 8.7 [95% CI 1.6-48.5], p for trend=0.005) [3].
• Risks of liver cancer, pancreatic cancer, and leukemia were not elevated among DDT-exposed workers [4].
• Cancer mortality was decreased among DDT-exposed workers, mainly due to a reduction in lung cancer deaths [4].

Psychiatry related information on Neocidol

• Nevertheless, the exposure to DDT during critical periods of human development--from conception to adolescence--and individual variations in metabolizing enzymes of DDT or its derivatives are still important areas to be researched in regard to breast cancer development in adulthood [5].
• Risk reduction for DDT toxicity and carcinogenesis through dietary modification [6].

High impact information on Neocidol

• CONCLUSION: p,p'-DDT is the most effective organochlorine in regulating estrogen receptor-mediated cellular responses [7].
• Chronic nervous-system effects of long-term occupational exposure to DDT [2].
• INTERPRETATION: Organochlorine compounds such as p,p'-DDT, p,p'-DDE, and some PCBs could play a part in the pathogenesis of exocrine pancreatic cancer through modulation of K-ras activation [3].
• There was no overall association between risk of breast cancer and p,p'-dichlorodiphenyltrichloroethane or metabolites or for polychlorinated biphenyls [8].
• These genes included the GST GSTE2, which has previously been implicated in dichlorodiphenyltrichloroethane resistance, two P450s, and two peroxidase genes [9].

Chemical compound and disease context of Neocidol

• Aerobic degradation of 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (DDT) by Alcaligenes eutrophus A5 [10].
• Contradicting published results regarding the relationship between body burden levels of p,p'-dichlorodiphenyldichloroethane (p,p'-DDE)--the main DDT metabolite--and breast cancer, we argue that such differences stem from methodologic differences among those studies [5].
• Changes in organochlorine concentrations were negatively associated with changes in serum T(3) concentration (significantly for p,p'-DDT, HCB, Aroclor 1260, PCB 28, PCB 99, PCB 118, and PCB 170) and with changes in RMR adjusted for weight loss (significantly for HCB and PCB 156) [11].
• The environmental estrogen, dichlorodiphenyltrichloroethane (DDT), and its metabolites have been implicated in the development of breast cancer through mechanisms that remain to be elucidated [12].
• Clonazepam (5-(2-chlorophenyl)-1,3-dihydro-7-nitro 2H-1,4 benzodiazepin-2-one) (2 mg/kg) reduced a p,p'-DDT-induced myoclonus in mice by 50% [13].

Biological context of Neocidol

• Statistical analysis (ANOVA model) identified 158 probe sets that were differentially transcribed among Rst(2)DDT(91-R), Rst(2)DDT(Wisconsin), and the DDT-susceptible genotype Canton-S (P < 0.01) [14].
• Several studies have evaluated cancer risk associated with occupational and environmental exposure to dichlorodiphenyltrichloroethane (DDT) [4].
• These results do not lend support to the hypothesis that DDT is causally related to breast cancer at the body-burden levels found in our study population but do not exclude the possibility that higher levels of exposure could still play a role in the etiology of this tumor [15].
• In terms of organic chemicals, the best known examples of bioaccumulation in aquatic food chains are the polychlorinated biphenyls (PCBs), dioxins, and organochlorine pesticides such as dichlorodiphenyltrichloroethane (DDT) [16].
• DDT treatment induces phosphorylation of ERK and p38, while JNK phosphorylation levels are slightly decreased [17].

Anatomical context of Neocidol

• These results showing that DDE, but not its parental compound, induces liver cell tumors in hamsters emphasize the importance of this metabolite as a proximal carcinogen of DDT [18].
• Treatment of WB-F344 rat liver epithelial cells with DDT (1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane) or lindane induces a loss of gap junction plaques and a decrease in the phosphorylated gap junction protein connexin43-P2 (Cx43-P2), which is associated with the plaques [19].
• In adult male mice, p,p'-DDT induced luciferase activity in liver, brain, thymus, and prostate but not in heart and lung [20].
• Pretreatment with phenytoin blocked p,p'-DDT-induced increases of aspartate in the brainstem and spinal cord, 5-HIAA in the hippocampus, and MHPG in the brainstem and hypothalamus [21].
• Due to its stability and its capacity to accumulate in adipose tissue, it is found in human tissues, and there is now not a single living organism on the planet that does not contain DDT [22].

Associations of Neocidol with other chemical compounds

• BACKGROUND: Organochlorines such as DDT [2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane] and PCBs (polychlorinated biphenyls), which have been used extensively as insecticides and as fluid insulators of electrical components, respectively, are known to be persistent environmental contaminants and animal carcinogens [23].
• Since hamsters appear to be resistant to tumor induction by DDT, we wanted to investigate whether DDE has any neoplastic effect in this species [18].
• Elevated risks were found, with odds ratio generally 1.5-fold or greater, for personal handling, mixing, or application of several pesticide groups and for individual insecticides, including carbaryl, chlordane, dichlorodiphenyltrichloroethane, diazinon, dichlorvos, lindane, malathion, nicotine, and toxaphene [24].
• Partial hepatectomy alone or in combination with phenobarbital, 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane or diethylstilbestrol produce liver tumors in trans-AAS pretreated rats [25].
• All environmental estrogenic chemicals [polychlorinated hydroxybiphenyls, dichlorodiphenyltrichloroethane (DDT) and derivatives, alkylphenols, bisphenol A, methoxychlor and chlordecone] compete with E2 for binding to both ER subtypes with a similar preference and degree [26].

Gene context of Neocidol

• The cytochrome P450 Cyp6a2 and the diazepam-binding inhibitor gene (Dbi) were over transcribed in the two DDT-resistant genotypes when compared to the wild-type Drosophila, and this difference was significant at the most stringent statistical level, a Bonferroni correction [14].
• Our results suggest that more than Cyp6g1 is overtranscribed in field and laboratory DDT-resistant genotypes, and the number of commonalities suggests that similar resistance mechanisms may exist between laboratory- and field-selected DDT-resistant fly lines [14].
• DDT stimulates an AP-1 complex shift at the DNA to one favoring c-Jun/c-Fos dimers through both increasing c-Jun levels and by post-translational activation of c-Jun and c-Fos in HEK 293 and human endometrial Ishikawa cells [17].
• The activity of catalase was increased in the PCB-fed rats but decreased after the administered of DDT [27].
• High dose p,p'-DDT (1000 but not 500 mg/kg), which also induced convulsions, only slightly increased 5-HT1 (unsubtyped) binding sites in cortex but not in brainstem or spinal cord and had no effect on antagonist-labelled 5-HT2 sites [28].

Analytical, diagnostic and therapeutic context of Neocidol

• Reproductive histories and other variables were obtained by structured interviews, DDT/DDE levels were determined in serum by gas-liquid chromatography [15].
• Dichlorodiphenyltrichloroethane serum levels and breast cancer risk: a case-control study from Mexico [15].
• Some, but not all, epidemiological studies have suggested that dichlorodiphenyltrichloroethane (DDT) may play a role in the development of breast cancer [15].
• Electrophysiological analysis of the myoclonus in the rat induced by p,p'-DDT revealed changes in EEG and EMG activity which suggested an origin for the myoclonus in the brainstem [29].
• Furthermore, their expressions under different concentrations of DDT treatment were detected by real-time fluorescent quantitative PCR [30].

References