Preneoplastic lesion

Yoshiji, H., Nakae, D., Mizumoto, Y., Horiguchi, K., Tamura, K., Denda, A., Tsujii, T. and Konishi, Y. (1992). Inhibitory effect of dietary iron deficiency on inductions of putative preneoplastic lesions as well as 8-hydroxydeoxyguanosine in DNA and lipid peroxidation in the livers of rats caused by exposure to a choline-deficient L-amino acid defined diet. Carcinogenesis 13, 1227-1233. 

Kobaek-Larsen M, Christensen L P, Vach W, Ritskes-Hoitinga J and Brandt K (2005), Inhibitory effects of feeding with carrots or (-) falcarinol on development of azomethane-induced preneoplastic lesions in the rat colon , J Agric Food Chem, 53, 1823-1827. 

Rizzi MB, Dagli ML, Jordao AA, Penteado MV and Moreno FS. 1997. Beta-carotene inhibits persistent and stimulates remodeling c-GT-positive preneoplastic lesions during early promotion of hepatocarcinogen-esis. Int J Vitam Nutr Res 67 415-422. 

In addition to their possible prooxidant activity (see above) polyphenols and flavonoids may influence cancer cells via their antioxidant properties. Recently, Jang et al. [219] studied cancer chemopreventive activity of resveratrol, a natural polyphenolic compound derived from grapes (Chapter 29). These authors showed that resveratrol inhibited the development of preneoplastic lesions in carcinogen-treated mouse mammary glands in culture and inhibited tumorigenesis in a mouse skin cancer model. Flavonoids silymarin and silibinin also exhibited antitumor-promoting effects at the stage I tumor promotion in mouse skin [220] and manifested antiproliferative effects in rat prostate cancer cells [221]. 

Evaluation of the data is not purely a statistical exercise. A number of important factors should be considered (1) dose-effect relationship (2) a shift towards more anaplastic tumors in organs where tumors are common (3) earlier appearance of tumors, and (4) presence of preneoplastic lesions. 

Rats exposed to di-n-octylphthalate in the diet for either 10 or 26 weeks following a single subcarcinogenic intraperitoneal injection of diethylnitrosamine and partial hepatectomy exhibited increases in GGT-positive liver foci that were not associated with peroxisome proliferation (Carter et al. 1992 DeAngelo et al. 1986). These results suggest that di-n-octy lph thal ate may be effective in promoting preneoplastic lesions in the rat liver, probably by a mechanism that does not rely on peroxisome proliferation. 

DeAngelo AB, Garrett CT, Manolukas LA, et al. 1986. Di-n-octyl phthalate (DOP), a relatively ineffective peroxisome inducing straight chain isomer of the environmental contaminant di(2-ethylhexyl)phthalate (DEHP), enhances the development of putative preneoplastic lesions in rat liver. Toxicology 41 279-288. 

The present results also point to differences between the mammary tumor model and the ACT model for evaluating the potential cancer protective effects of Se in broccoli. A previous study (17) showed that high-Se broccoli florets decreased the number of DMH-induced ACT. Similarly, in the present study high-Se broccoli sprouts decreased DMH-induced ACT, but low-Se broccoli sprouts alone did not have any effect (Table 3). In the mammary tumor model, however, broccoli alone, similar to garlic alone (3), reduced the number of tumors (Table 1). This contrasting effect could be the result of a difference between tumor and preneoplastic lesion models, a difference between carcinogens, or a difference between mammary and colonic tissues. 

Administered in the drinking water for 113 weeks, 42mg/l crotonaldehyde induced neoplastic lesions in rats 2 of 27 animals had hepatocellular carcinomas and 9 of 27 had neoplastic lesions. Altered liver cell foci occurred in 23 of the 27 animals. The increased incidence of neoplastic and preneoplastic lesions was not observed at the higher dose (421 mg/1). Crotonaldehyde produced variable results in a variety of genetic assays. ... 

Shirahama T. Cyclooxygenase-2 expression is up-regulated in transitional cell carcinoma and its preneoplastic lesions in the human urinary bladder. Clin Cancer Res 2000 6 2424—2430. 

Epidemiological studies of benign neoplasms, presumed preneoplastic lesions and other end-points thought to be relevant to cancer are also reviewed by working groups. They may, in some instances, strengthen inferences drawn from studies of cancer itself... 

Other evidence judged to be relevant to an evaluation of carcinogenicity and of sufficient importance to affect the overall evaluation is then described. This may include data on preneoplastic lesions, tumour pathology, genetic and related effects, structure-activity relationships, metabolism and pharmacokinetics, physicochemical parameters and analogous biological agents. 

Medina, D. (1976). "Preneoplastic lesions in murine mammary canca Cancer Res. 36,2589. 

Some information on structure-promotion relationships for PBBs is available from studies that used two-stage liver and skin carcinogenesis models. In the liver promotion studies, development of enzyme-altered hepatic foci (putative preneoplastic lesions) was assessed in rats that were partially hepatectomized, initiated with diethylnitrosamine and promoted with PBBs (Buchmann et al. 1991 Dixon et al. 1988 ... 

Rangga-Tabbu C, Sleight SD. 1992. Development of preneoplastic lesions in the liver and nasal epithelium of rats initiated with N-nitrosodimethylamine or N-nitrosopyrrolidine and promoted with polybrominated biphenyls. Food Chem Toxicol 30( 11) 921 -926. 

Evidence of preneoplastic lesions in repeated-dose toxicity studies... 

Data relevant to an evaluation of carcinogenicity in animals are summarized. For each animal species and route of administration, it is stated whether an increased incidence of neoplasms or preneoplastic lesions was observed, and the tumoiu sites are indicated. If the agent or mixture produced tumours after prenatal exposure or in singledose experiments, this is also indicated. Negative findings are also summarized. Dose-response and other quantitative data may be given when available. 

Ying, T.S., Sarma, D.S. Farber, E. (1979) Induction of presumptive preneoplastic lesions in rat liver by a single dose of 1,2-dimethylhydrazine. Chem.-biol. Inter., 28, 363-366... 

Moore, M.A., Tsuda, H., Thamavit, W., Masui, T. Ito, N. (1987) Differential modification of development of preneoplastic lesions in the Syrian golden hamster initiated with a single dose of 2,2 -dioxo-V-nitrosodipropylamine influence of subsequent butylated hydroxyanisole, alpha-tocopherol, or carbazole. J. natl Cancer Inst., 78,289-293... 

Calore, E. E., Cavahere, M. J., Calore, N. M. P., Dias, s.d.s., Paes. dos santos, R, Vitela-de-Almeida, L. 2001. Expression of ki-67 in cervical epithelial cells in preneoplastic lesions of patients with AIDS. Gynecol. Obstet. Invest. 57 51-54. 

In repeated-dose toxicity studies when a dosing duration adequate for evaluation is attained, no preneoplastic lesions are observed. 

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