Altered foci of hepatocytes in rats initiated with diethylnitrosamine after prolonged fasting

Assessment of genotoxicity induced by 7,12‐dimethylbenz(a)anthracene or diethylnitrosamine in the Pig‐a, micronucleus and Comet assays integrated into 28‐day repeat dose studies

“…It is a well known hepatocarcinogen and causes tumors in multiple organs such as kidney, esophagus, and vascular systems, in addition to the liver. DEN is metabolized by mixed-function cytochrome P-450 dependent oxidase systems and the derived intermediates are highly reactive and directly responsible for inducing mutation and the onset of cancer [Schmitt et al, 1993]. DEN is a strong genotoxin in in vitro systems, as it has been determined to be positive in Ames, MLA, CHO HPRT mutation assays [Toxnet].…”

Assessment of genotoxicity induced by 7,12‐dimethylbenz(a)anthracene or diethylnitrosamine in the Pig‐a, micronucleus and Comet assays integrated into 28‐day repeat dose studies

“…It is a well known hepatocarcinogen and causes tumors in multiple organs such as kidney, esophagus, and vascular systems, in addition to the liver. DEN is metabolized by mixed-function cytochrome P-450 dependent oxidase systems and the derived intermediates are highly reactive and directly responsible for inducing mutation and the onset of cancer [Schmitt et al, 1993]. DEN is a strong genotoxin in in vitro systems, as it has been determined to be positive in Ames, MLA, CHO HPRT mutation assays [Toxnet].…”

Protective effect of Cassia fistula Linn. on diethylnitrosamine induced hepatocellular damage and oxidative stress in ethanol pretreated rats

“…DEN is biotransformed by mixed-function cytochrome P-450 dependent monooxidase systems and its metabolic activation is reported to be responsible for the onset of the toxic effects (Zimmerman, 1993). Intermediate reactive compounds originating from the bioactivation of DEN are known to form covalent bonds with important cell constituents, thus inducing the onset of mutations, cancer, and necrosis (Schmitt et al, 1993). Microsomal activation of DEN involves cytochrome P450 2E1 and hence compounds that selectively activate cytochrome P450 systems are being widely used by several investigators to induce hepatocellular carcinoma in experimental animals.…”

The effect of short-term fasting, phenobarbital and refeeding on apoptotic loss, cell replication and gene expression in rat liver during the promotion stage

“…Recently, Grasl-Kraupp et al (16) and James and Muskhelishvili (5) demonstrated that apoptosis may play an important role in the inhibitory effects of chronic caloric restriction on spontaneous hepatocarcinogenesis. In contrast, relatively little is known at present about the influences of acute fasting on the carcinogenic process (17)(18)(19) and neoplastic growth (20). Schmitt et al reported that 2 days of fasting did not influence the initiation stage of hepatocarcinogenesis (17).…”

“…In contrast, relatively little is known at present about the influences of acute fasting on the carcinogenic process (17)(18)(19) and neoplastic growth (20). Schmitt et al reported that 2 days of fasting did not influence the initiation stage of hepatocarcinogenesis (17). However, short-term fasting was found to sustain the initiated cells (19) and to enhance promotion effects (18), such as compensatory cell proliferation (21,22), in the early stages of hepatocarcinogenesis.…”

Assessment of genotoxicity induced by 7,12‐dimethylbenz(a)anthracene or diethylnitrosamine in the Pig‐a, micronucleus and Comet assays integrated into 28‐day repeat dose studies

“…It is a well known hepatocarcinogen and causes tumors in multiple organs such as kidney, esophagus, and vascular systems, in addition to the liver. DEN is metabolized by mixed-function cytochrome P-450 dependent oxidase systems and the derived intermediates are highly reactive and directly responsible for inducing mutation and the onset of cancer [Schmitt et al, 1993]. DEN is a strong genotoxin in in vitro systems, as it has been determined to be positive in Ames, MLA, CHO HPRT mutation assays [Toxnet].…”

Protective effect of Cassia fistula Linn. on diethylnitrosamine induced hepatocellular damage and oxidative stress in ethanol pretreated rats

“…DEN is biotransformed by mixed-function cytochrome P-450 dependent monooxidase systems and its metabolic activation is reported to be responsible for the onset of the toxic effects (Zimmerman, 1993). Intermediate reactive compounds originating from the bioactivation of DEN are known to form covalent bonds with important cell constituents, thus inducing the onset of mutations, cancer, and necrosis (Schmitt et al, 1993). Microsomal activation of DEN involves cytochrome P450 2E1 and hence compounds that selectively activate cytochrome P450 systems are being widely used by several investigators to induce hepatocellular carcinoma in experimental animals.…”

The effect of short-term fasting, phenobarbital and refeeding on apoptotic loss, cell replication and gene expression in rat liver during the promotion stage

“…Recently, Grasl-Kraupp et al (16) and James and Muskhelishvili (5) demonstrated that apoptosis may play an important role in the inhibitory effects of chronic caloric restriction on spontaneous hepatocarcinogenesis. In contrast, relatively little is known at present about the influences of acute fasting on the carcinogenic process (17)(18)(19) and neoplastic growth (20). Schmitt et al reported that 2 days of fasting did not influence the initiation stage of hepatocarcinogenesis (17).…”

“…In contrast, relatively little is known at present about the influences of acute fasting on the carcinogenic process (17)(18)(19) and neoplastic growth (20). Schmitt et al reported that 2 days of fasting did not influence the initiation stage of hepatocarcinogenesis (17). However, short-term fasting was found to sustain the initiated cells (19) and to enhance promotion effects (18), such as compensatory cell proliferation (21,22), in the early stages of hepatocarcinogenesis.…”

Assessment of genotoxicity induced by 7,12‐dimethylbenz(a)anthracene or diethylnitrosamine in the Pig‐a, micronucleus and Comet assays integrated into 28‐day repeat dose studies

“…It is a well known hepatocarcinogen and causes tumors in multiple organs such as kidney, esophagus, and vascular systems, in addition to the liver. DEN is metabolized by mixed-function cytochrome P-450 dependent oxidase systems and the derived intermediates are highly reactive and directly responsible for inducing mutation and the onset of cancer [Schmitt et al, 1993]. DEN is a strong genotoxin in in vitro systems, as it has been determined to be positive in Ames, MLA, CHO HPRT mutation assays [Toxnet].…”

Protective effect of Cassia fistula Linn. on diethylnitrosamine induced hepatocellular damage and oxidative stress in ethanol pretreated rats

“…DEN is biotransformed by mixed-function cytochrome P-450 dependent monooxidase systems and its metabolic activation is reported to be responsible for the onset of the toxic effects (Zimmerman, 1993). Intermediate reactive compounds originating from the bioactivation of DEN are known to form covalent bonds with important cell constituents, thus inducing the onset of mutations, cancer, and necrosis (Schmitt et al, 1993). Microsomal activation of DEN involves cytochrome P450 2E1 and hence compounds that selectively activate cytochrome P450 systems are being widely used by several investigators to induce hepatocellular carcinoma in experimental animals.…”

The effect of short-term fasting, phenobarbital and refeeding on apoptotic loss, cell replication and gene expression in rat liver during the promotion stage

“…Recently, Grasl-Kraupp et al (16) and James and Muskhelishvili (5) demonstrated that apoptosis may play an important role in the inhibitory effects of chronic caloric restriction on spontaneous hepatocarcinogenesis. In contrast, relatively little is known at present about the influences of acute fasting on the carcinogenic process (17)(18)(19) and neoplastic growth (20). Schmitt et al reported that 2 days of fasting did not influence the initiation stage of hepatocarcinogenesis (17).…”

“…In contrast, relatively little is known at present about the influences of acute fasting on the carcinogenic process (17)(18)(19) and neoplastic growth (20). Schmitt et al reported that 2 days of fasting did not influence the initiation stage of hepatocarcinogenesis (17). However, short-term fasting was found to sustain the initiated cells (19) and to enhance promotion effects (18), such as compensatory cell proliferation (21,22), in the early stages of hepatocarcinogenesis.…”