The effects of long-term oral administration of ethanol on Sprague-Dawley rats — a condensed report

Existence of No Hepatocarcinogenic Effect Levels of 2-amino-3,8-dimethylimidazo[4,5- f ]quinoxaline with or without Coadministration with Ethanol

“…However, the exact mechanisms of alcohol carcinogenicity remain unclear. In experimental animal studies, ethanol per se has not been found to induce liver tumors but rather to promote chemically induced hepatocarcinogenesis (Porta et al, 1985; Takada et al, 1986; Tanaka et al, 1989; Holmberg and Ekstrom, 1995; Poschl and Seitz, 2004). We have previously proposed that treatment with ethanol might promote 10 ppm MeIQx-induced hepatocarcinogenesis through elevated cell proliferation and oxidative stress (Karim et al, 2003).…”

Existence of No Hepatocarcinogenic Effect Levels of 2-amino-3,8-dimethylimidazo[4,5- f ]quinoxaline with or without Coadministration with Ethanol

“…However, the exact mechanisms of alcohol carcinogenicity remain unclear. In experimental animal studies, ethanol per se has not been found to induce liver tumors but rather to promote chemically induced hepatocarcinogenesis (Porta et al, 1985; Takada et al, 1986; Tanaka et al, 1989; Holmberg and Ekstrom, 1995; Poschl and Seitz, 2004). We have previously proposed that treatment with ethanol might promote 10 ppm MeIQx-induced hepatocarcinogenesis through elevated cell proliferation and oxidative stress (Karim et al, 2003).…”

Understanding the Role of Connexins in Hepatocellular Carcinoma: Molecular and Prognostic Implications

“…Towards this direction, Kato et al aimed to correlate ethanol consumption with Cx32 expression in HCC [73]. In vivo, ethanol treatment has been shown to enhance chemically induced hepatocarcinogenesis using animal models; however, other studies dispute this statement, and the detailed molecular mechanisms by which ethanol contributes to hepatocarcinogenesis has not been established yet [144][145][146]. Kato et al, using mouse models, and specifically Cx32 dominant negative transgenic (Tg) and wild-type (Wt) mouse models which were given 1 or 5% ethanol or water ad libitum for 16 weeks after an intraperitoneal injection of 200 mg/kg diethyl nitrosamine, suggested that dysregulated Cx32 expression may promote ethanol-related hepatocarcinogenesis, and that Cx32 dysfunction compared with exposure to ethanol decreases Dusp1 expression leading to Erk activation in glutathione S-transferase placental form (GST-P)-positive foci, enhancing tumorigenic activity [73].…”

In Vivo and In Vitro Models of Hepatocellular Carcinoma: Current Strategies for Translational Modeling

“…According to IARC, there is sufficient evidence in both humans and experimental animal models to substantiate the carcinogenicity of ethanol since this toxin is classified in group 1 [ 28 ]. Nonetheless, a very low frequency of neoplastic alterations is observed in long-term intervention in rats [ 178 ]. In mice, a statistical trend was observed in 2-year-long ethanol intervention in drinking water regarding the incidence of neoplastic lesions, mainly adenomas [ 179 ].…”

Existence of No Hepatocarcinogenic Effect Levels of 2-amino-3,8-dimethylimidazo[4,5- f ]quinoxaline with or without Coadministration with Ethanol

“…However, the exact mechanisms of alcohol carcinogenicity remain unclear. In experimental animal studies, ethanol per se has not been found to induce liver tumors but rather to promote chemically induced hepatocarcinogenesis (Porta et al, 1985; Takada et al, 1986; Tanaka et al, 1989; Holmberg and Ekstrom, 1995; Poschl and Seitz, 2004). We have previously proposed that treatment with ethanol might promote 10 ppm MeIQx-induced hepatocarcinogenesis through elevated cell proliferation and oxidative stress (Karim et al, 2003).…”

Understanding the Role of Connexins in Hepatocellular Carcinoma: Molecular and Prognostic Implications

“…Towards this direction, Kato et al aimed to correlate ethanol consumption with Cx32 expression in HCC [73]. In vivo, ethanol treatment has been shown to enhance chemically induced hepatocarcinogenesis using animal models; however, other studies dispute this statement, and the detailed molecular mechanisms by which ethanol contributes to hepatocarcinogenesis has not been established yet [144][145][146]. Kato et al, using mouse models, and specifically Cx32 dominant negative transgenic (Tg) and wild-type (Wt) mouse models which were given 1 or 5% ethanol or water ad libitum for 16 weeks after an intraperitoneal injection of 200 mg/kg diethyl nitrosamine, suggested that dysregulated Cx32 expression may promote ethanol-related hepatocarcinogenesis, and that Cx32 dysfunction compared with exposure to ethanol decreases Dusp1 expression leading to Erk activation in glutathione S-transferase placental form (GST-P)-positive foci, enhancing tumorigenic activity [73].…”

In Vivo and In Vitro Models of Hepatocellular Carcinoma: Current Strategies for Translational Modeling

“…According to IARC, there is sufficient evidence in both humans and experimental animal models to substantiate the carcinogenicity of ethanol since this toxin is classified in group 1 [ 28 ]. Nonetheless, a very low frequency of neoplastic alterations is observed in long-term intervention in rats [ 178 ]. In mice, a statistical trend was observed in 2-year-long ethanol intervention in drinking water regarding the incidence of neoplastic lesions, mainly adenomas [ 179 ].…”

Existence of No Hepatocarcinogenic Effect Levels of 2-amino-3,8-dimethylimidazo[4,5- f ]quinoxaline with or without Coadministration with Ethanol

“…However, the exact mechanisms of alcohol carcinogenicity remain unclear. In experimental animal studies, ethanol per se has not been found to induce liver tumors but rather to promote chemically induced hepatocarcinogenesis (Porta et al, 1985; Takada et al, 1986; Tanaka et al, 1989; Holmberg and Ekstrom, 1995; Poschl and Seitz, 2004). We have previously proposed that treatment with ethanol might promote 10 ppm MeIQx-induced hepatocarcinogenesis through elevated cell proliferation and oxidative stress (Karim et al, 2003).…”

Understanding the Role of Connexins in Hepatocellular Carcinoma: Molecular and Prognostic Implications

“…Towards this direction, Kato et al aimed to correlate ethanol consumption with Cx32 expression in HCC [73]. In vivo, ethanol treatment has been shown to enhance chemically induced hepatocarcinogenesis using animal models; however, other studies dispute this statement, and the detailed molecular mechanisms by which ethanol contributes to hepatocarcinogenesis has not been established yet [144][145][146]. Kato et al, using mouse models, and specifically Cx32 dominant negative transgenic (Tg) and wild-type (Wt) mouse models which were given 1 or 5% ethanol or water ad libitum for 16 weeks after an intraperitoneal injection of 200 mg/kg diethyl nitrosamine, suggested that dysregulated Cx32 expression may promote ethanol-related hepatocarcinogenesis, and that Cx32 dysfunction compared with exposure to ethanol decreases Dusp1 expression leading to Erk activation in glutathione S-transferase placental form (GST-P)-positive foci, enhancing tumorigenic activity [73].…”

In Vivo and In Vitro Models of Hepatocellular Carcinoma: Current Strategies for Translational Modeling

“…According to IARC, there is sufficient evidence in both humans and experimental animal models to substantiate the carcinogenicity of ethanol since this toxin is classified in group 1 [ 28 ]. Nonetheless, a very low frequency of neoplastic alterations is observed in long-term intervention in rats [ 178 ]. In mice, a statistical trend was observed in 2-year-long ethanol intervention in drinking water regarding the incidence of neoplastic lesions, mainly adenomas [ 179 ].…”