[논문]Toxicity and Carcinogenicity of Dichlorodiphenyltrichloroethane (DDT)

Harada, Takanori; Takeda, Makio; Kojima, Sayuri; Tomiyama, Naruto

doi:10.5487/tr.2016.32.1.021

Toxicity and Carcinogenicity of Dichlorodiphenyltrichloroethane (DDT) 원문보기

Toxicological research, v.32 no.1, 2016년, pp.21 - 33

Harada, Takanori (The Institute of Environmental Toxicology) , Takeda, Makio (The Institute of Environmental Toxicology) , Kojima, Sayuri (The Institute of Environmental Toxicology) , Tomiyama, Naruto (The Institute of Environmental Toxicology)

Abstract ▼ AI-Helper

Dichlorodiphenyltrichloroethane (DDT) is still used in certain areas of tropics and subtropics to control malaria and other insect-transmitted diseases. DDT and its metabolites have been extensively studied for their toxicity and carcinogenicity in animals and humans and shown to have an endocrine disrupting potential affecting reproductive system although the effects may vary among animal species in correlation with exposure levels. Epidemiologic studies revealed either positive or negative associations between exposure to DDT and tumor development, but there has been no clear evidence that DDT causes cancer in humans. In experimental animals, tumor induction by DDT has been shown in the liver, lung, and adrenals. The mechanisms of hepatic tumor development by DDT have been studied in rats and mice. DDT is known as a non-genotoxic hepatocarcinogen and has been shown to induce microsomal enzymes through activation of constitutive androstane receptor (CAR) and to inhibit gap junctional intercellular communication (GJIC) in the rodent liver. The results from our previously conducted 4-week and 2-year feeding studies of p,p'-DDT in F344 rats indicate that DDT may induce hepatocellular eosinophilic foci as a result of oxidative DNA damage and leads them to hepatic neoplasia in combination with its mitogenic activity and inhibitory effect on GJIC. Oxidative stress could be a key factor in hepatocarcinogenesis by DDT.

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문제 정의

Our previously conducted 4-week and 2-year feeding studies of p,p'-DDT in F344 rats were supported by a grant from the Ministry of Agriculture, Forestry and Fisheries. We are grateful to our colleagues in the Toxicology and Chemictry Divisions of the Institute of Environmental Toxicology for their valuable suggestions, cooperation and/or technical support in this work.

제안 방법

The toxic changes caused by DDT in the liver and potential factors involved in hepatocarcinogenesis by DDT are discussed in the following sections on the basis of the results obtained from our previously conducted 4-week feeding study of p,p'-DDT in male F344 rats at 0, 50, 160, 500 ppm and 2-year feeding study of p,p'-DDT in F344 rats of both sexes at 0, 5, 50, 500 ppm (5).

성능/효과

The results are generally consistent with previous works (14-17,23-25) and considered due to activation of constitutive androstane receptor (CAR) (24). As shown in Tables 1~3, the increases in CYP2B1 and CYP3A2 were dose-dependent, whereas the elevation of PROD activity was most evident in the mid-dose group and not significant in males of the high-dose group after 52, 78, and 104 weeks. This suggests that microsomal enzyme activity is not always consistent with its associated protein content and there seems to be an almost inverse correlation between the increase in PROD at different time points and the concurrent incidence of pre-neoplastic hepatocellular eosinophilic foci and hepatocellular tumors.
Based on these results, it was concluded that the in vivo effects of p,p'-DDT associated with its endocrine activities are not adverse at least under the experimental condition and thus p,p'-DDT is not considered to exert overt endocrine disrupting effects in SD rats at levels up to 350 ppm.

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