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Connexin32 knockout mice (Cx32-KO) exhibit increased chemical- and radiation-induced liver and lung tumor formation with many lung tumors demonstrating decreased levels of the tumor suppressor p27KIP1. To determine if p27 deficiency alters Cx32-influenced tumorigenesis, we have generated a Cx32/p27 double-deficient mouse strain (DKO) and show here that exposure of these mice to X-ray radiation resulted in an increase or decrease in tumorigenesis depending on the tissue. Several tissues were highly sensitive to loss of p27 tumor suppressor function (intestine, adrenal, pituitary) resulting in an increased overall tumor burden in DKO mice compared to both wild-type (P<0.005) and Cx32-KO mice (P=0.066). However, additional deletion of p27 in a Cx32-KO background resulted in a statistically significant decrease in the liver tumor incidence suggesting that Cx32 and p27 pathways mechanistically interact. Immunohistochemical analysis revealed an increased percentage of Cx32-KO liver and lung tumors harboring active mitogen-activated protein kinase (Erk1, Erk2) pathways in contrast to lower percentages of activated wild-type (P<0.005) and DKO tumors (P=0.027). Increased MAPK activation in liver tumors did not correlate with Ha-ras codon-61 mutation status. This study demonstrates that tissues dependent on Cx32 tumor suppression, such as the liver and lung, exhibit altered tumorigenesis and tumor biology (MAPK pathway activation) related to p27 status.Oncogene (2005) 24, 1718-1726. doi:10.1038/sj.onc.1208355 Published online 31 January 2005 [ABSTRACT FROM AUTHOR]

beta-glucuronidase, an acid hydrolase that deconjugates glucuronides, may increase cancer risk; however, little is known about factors associated with human beta -glucuronidase. Our objective was to examine whether dietary and demographic factors were associated with serum beta -glucuronidase activity. We conducted a cross-sectional study among 279 healthy men and women aged 20 to 40 yr. Diet, categorized by botanical families and nutrient intakes, was assessed from 3-day food records and a validated semiquantitative food frequency questionnaire. Demographic factors were directly measured or self-reported. Adjusted mean beta -glucuronidase activity across categories of exposure variables were calculated by multiple linear regression. Higher beta -glucuronidase activity was significantly associated with being male, older age (> or = 30 yr), non-Caucasian, overweight (> or = 25 kg/m(2)), and higher intakes of gamma-tocopherol. Conversely, lower beta -glucuronidase activity was significantly associated with higher intakes of calcium, iron, and magnesium. A suggestive decrease in beta -glucuronidase activity was observed for the botanical families Cruciferae, Rutaceae, Compositae, Roseaceae, and Umbelliferae, but tests for trend were not statistically significant. In conclusion, several dietary and nondietary factors were associated with beta -glucuronidase activity; however, confirmation of these associations are needed.

Enterolactone is a lignan produced by fermentation of dietary precursors in the human gut. Because lignan precursors are uniquely found in plant foods, plasma enterolactone concentration may serve as a biological marker of plant food consumption. This cross-sectional study examined associations of dietary intake with plasma enterolactone concentration. Weight-stable, 20-40-year-old volunteers (115 women and 78 men in Seattle, Washington) reporting intake of < or =2.5 or > or =4.5 fruit and vegetable servings/day and no antibiotic use for > or =3 months completed a food frequency questionnaire and 3-day food record. Time-resolved fluoroimmunoassay was used to measure plasma enterolactone. Based on diet records, plasma enterolactone was positively correlated with daily vegetable servings (r = 0.17; P < 0.05), fiber (r = 0.36; P < 0.0001), alcohol (r = 0.24; P < 0.001), caffeine (r = 0.21; P < 0.001), and daily botanical group servings [Chenopodiaceae (r = 0.15; P < 0.05), Juglandaceae (r = 0.15; P < 0.05), Leguminosae (r = 0.20; P < 0.001), Pedaliaceae (r = 0.20; P < 0.001), and Vitaceae (r = 0.20; P < 0.001)]. Fat-related variables were not correlated with plasma enterolactone. Based on linear regression models, plasma enterolactone increased by 37.0% (SE = 2.3%) for each 10-g increase in fiber and by 6.6% (SE = 0.2%) for each 50-mg serving of caffeine. Participants consuming 0.5-1 alcoholic drink/day had plasma enterolactone concentrations that were 131.4% (SE = 37.6%) higher than those of nondrinkers. Although plasma enterolactone may be useful as a biological measure of exposure to lignan-containing foods, it may be of limited use as a specific biomarker of fruit and vegetable or plant food intake because coffee, tea, and alcoholic beverages also significantly increase its plasma concentration.