CANCER BIOLOGY: Reversibility of promoter induced hepatic focal lesion growth in mice

Abstract

The effect of cessation of phenobarbital and dieldren treatment on hepatic focal lesion growth in male B6C3F1 mice was investigated. Following induction of lesions by diethylnitrosamine, mice were placed on control NIH-07 diet (control diet) or NIH-07 diet containing either dieldrin (10.0 mg/kg diet) or phenobarbital (500 mg/kg diet). Mice were sacrificed after 30 and 60 days of dietary treatment. Two additional groups of mice were fed either the dieldren- or phenobarbital-containing diet for 30 days followed by feeding of NIH-07-only diet for an additional 30 days. The effect of treatment and removal of dieldrin or phenobarbital on lesion growth was examined by measuring both the number of focal lesions per liver and the relative volume of focal lesions. In addition, the rate of cell proliferation and programmed cell death in focal lesion growth was investigated by examining DNA synthesis and apoptosis in the focal lesions. Dietary dieldrin or phenobarbital increased the number of focal lesions and the focal lesion volume. In both dieldrin- and phenobarbital-treated mice, an increased number of eosinophilic lesions were seen. The focal lesion volume was increased in both eosinophilic and basophilic lesions. Dieldrin and phenobarbital treatment also increased the DNA synthetic labeling index in both eosinophilic and basophilic lesions. Removal of dieldrin or phenobarbital from the diet after 30 days of promoter treatment decreased the total number and volume of hepatic focal lesions. The labeling index of the focal lesions was also decreased in these mice. At the terminal sacrifice, the percentage of apoptotic cells in focal lesions was higher in mice fed dieldrin- or phenobarbital-containing diets for the entire 60 days than in mice returned to control diet for the last 30 days. Eosinophilic lesions were more dependent on the presence of a promoting stimulus than the basophilic lesions. These data indicate that induction and maintenance of the growth of some preneoplastic lesions in the mouse may be dependent upon continuous tumor promoter treatment.

Aldrin and Dieldrin: A Review of Research on Their Production, Environmental Deposition and Fate, Bioaccumulation, Toxicology, and Epidemiology in the United States

“…Studies of DDT and dieldrin on liver-promoting/hepatocarcinogenic actions show a strong correlation affecting gap junction-mediated intercellular communication in mice and rats liver tumors. In mice fed a diet of 10.0 mg/kg of dieldrin for 30 and 60 days, the number and volume of focal liver lesions and eosinophilic lesions increased as dieldrin was continued in the diet and subsided as dieldrin was removed (120).…”

18F-FLT and 18F-FDG PET-CT imaging in the evaluation of early therapeutic effects of chemotherapy on Walker 256 tumor-bearing rats

“…This agent reflects glucose metabolism in organs and tissues and thereby is widely used in tumor diagnosis, staging, curative effect determination, and recurrence monitoring (2). However, some metabolically active tissues or lesions, including the myocardium, brain tissue, inflammatory areas, and certain benign tumors, may also exhibit increased uptake of imaging agents, leading to poor 18 F-FDG imaging specificity (2). Previous preclinical and clinical studies have shown that F-18-fluoro-3'-deoxy-3'-L-fluorothymidine ( 18 F-FLT), which is a pyrimidine analogue, reflects changes in the tumor cell proliferative activity and its uptake in tumor tissues is associated with this activity (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13).…”

“…Previous preclinical and clinical studies have shown that F-18-fluoro-3'-deoxy-3'-L-fluorothymidine ( 18 F-FLT), which is a pyrimidine analogue, reflects changes in the tumor cell proliferative activity and its uptake in tumor tissues is associated with this activity (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). Therefore, 18 F-FLT may be used as a positron imaging agent for early evaluation of the curative effects of therapies on tumors. However, some studies have indicated that there may not be an association between 18 F-FLT uptake and tumor cell proliferative activity (14,15).…”

“…Therefore, 18 F-FLT may be used as a positron imaging agent for early evaluation of the curative effects of therapies on tumors. However, some studies have indicated that there may not be an association between 18 F-FLT uptake and tumor cell proliferative activity (14,15).…”

“…Although 18 F-FLT shares some biochemical characteristics with thymidine, it serves as a terminator of DNA strand synthesis and is not incorporated into the DNA strand. In addition, the dynamic differences between 18 F-FLT and thymidine have not yet been clearly defined (16).…”