Alcohol-Stimulated Promotion of Tumors in the Gastrointestinal Tract

Abstract

Alcohol is a major risk factor for cancers of the upper gastrointestinal tract but the association with cancers of the large bowel is not as clearly established. In recent studies, we have provided experimental support for the associations in the esophagus and oral cavity. Our studies also indicate that the tumor promotion ability of ethanol is related to its ability to generate oxygen free radicals as measured by an increase in indices of lipid peroxidation. This increase in lipid peroxidation was evident in the liver as well as the tissues targeted by the site-specific carcinogens and promoted by ethanol. Studies in mice showed that the increased lipid peroxidation as well as tumor incidence was inhibited by the administration of vitamin E, the potent antioxidant. Determination of fatty acid profiles showed significant alterations when ethanol was used as a tumor promoter after treatment with the carcinogen. Ethanol as a promoter caused an increase in esophageal polyunsaturated fatty acids (PUFA). Ethanol promotion was also evident in increased arachidonate and an exaggeration in PUFA that are involved in eicosanoid production. Thus, these results suggest that ethanol-related promotion may be the result of excessive cell proliferation induced by disordered lipid and eicosanoid metabolism that may cause a selective outgrowth of the carcinogen-initiated cells. Supporting evidence for ethanol-induced hyper-regeneration is also reviewed.

Exploring the mechanisms of alcohol-related damage in oral mucosa – is oxidative stress associated with the increase in cell proliferation in rat tongue epithelium?

“…Additionally, taking the oxidative parameter analyses into account, it can be suggested that the damage in oral mucosa is cumulative and progressive. Our findings may only support the hypothesis that alcohol acts as a promoter, and not as an initiator, of oral cancer (Mufti, 1998). Nevertheless, the increase in cell proliferation may be the first step in oral carcinogenesis, since fast turnover tissues are more susceptible to DNA duplication errors (Melnick et al, 1993;Tomatis, 1993).…”

Ethanol‐induced in vitro invasion of breast cancer cells: The contribution of MMP‐2 by fibroblasts

“…Alcohol is a tumor promoter; there is a positive correlation between alcohol intake and the risk of several human cancers, including mouth/oropharyngeal cancer, oesophageal cancer, liver cancer and breast cancer. [3][4][5][6][7][8][9][10][11] Epidemiologic studies indicate that alcohol consumption is associated with advanced and invasive breast tumors, [12][13][14] suggesting that alcohol may enhance tumor development and metastasis. These epidemiologic results are supported by experimental studies using animal models and cell culture systems, which show that ethanol promotes mammary tumorigenesis and stimulates proliferation as well as invasion of breast cancer cells.…”

Abrogation of hepatocyte apoptosis and early appearance of liver dysplasia in ethanol-fed p53-deficient mice

“…Ethanol consumption is causally linked to several human neoplasms, including primitive liver cancer [2]. Alcohol metabolism in liver cells leads to the formation of reactive oxygen species (ROS), which are responsible for hepatocyte damage, cellular apoptosis, and inflammation associated to excess alcohol consumption [3,4].…”