Milk intake in early life and risk of advanced prostate cancer

The authors investigated whether early-life residency in certain areas of Iceland marked by distinct differences in milk intake was associated with risk of prostate cancer in a population-based cohort of 8,894 men born between 1907 and 1935. Through linkage to cancer and mortality registers, the men were followed for prostate cancer diagnosis and mortality from study entry (in waves from 1967 to 1987) through 2009. In 2002-2006, a subgroup of 2,268 participants reported their milk intake in early, mid-, and current life. During a mean follow-up period of 24.3 years, 1,123 men were diagnosed with prostate cancer, including 371 with advanced disease (stage 3 or higher or prostate cancer death). Compared with early-life residency in the capital area, rural residency in the first 20 years of life was marginally associated with increased risk of advanced prostate cancer (hazard ratio = 1.29, 95% confidence interval (CI): 0.97, 1.73), particularly among men born before 1920 (hazard ratio = 1.64, 95% CI: 1.06, 2.56). Daily milk consumption in adolescence (vs. less than daily), but not in midlife or currently, was associated with a 3.2-fold risk of advanced prostate cancer (95% CI: 1.25, 8.28). These data suggest that frequent milk intake in adolescence increases risk of advanced prostate cancer.     

Increased gene specific repair of cisplatin induced interstrand crosslinks in cisplatin resistant cell lines, and studies on carrier ligand specificity

Development of resistance to cisplatin in previously treatment-responsivemalignancies is a major obstacle to successful treatment. EnhancedDNA repair as well as enhanced replicative bypass of DNA adductshave been suggested to play a role in the development of resistanceto cisplatin. However, the relative contribution of these mechanismsis unknown. Second generation platinum compounds containingthe 1, 2-diaminocyclohexane (dach) carrier ligand have beenof particular interest in the studies of resistance mechanismssince they have been effective in treatment of cells resistantto cisplatin. We have investigated the formation and repairof interstrand crosslinks (ICL) in the mouse leukemia cell lineLI 210/0 and its carrier ligand specific resistant derivativesL1210/DDP and L1210/ DACH after treatment with ethylenediamine(en)-Pt and diaminocyclohexane (dach)-Pt compounds. ICL in theoverall genome were examined using a modification of the alkalineelution assay. A Southern blot technique was employed for thestudy of ICL in specific regions of the genome. In the overallgenome we found decreased formation of ICL with either -en or-dach carrier ligands in the two resistant cell lines withoutcarrier ligand specificity. Some carrier ligand specificityof ICL formation was observed in the dihydrofolate reductase(DHFR) gene, but it did not correlate with the carrier ligandspecificity of resistance. At the level of the overall genomethere was no difference in repair of ICL between the sensitiveand the two resistant cell lines. When measured in the DHFRgene, however, there was enhanced repair of ICL in the two resistantcell lines compared with the sensitive cell line. The enhancedrepair at the level of the gene did not display any carrierligand specificity.     

Diet,pregnancy, and lactation: Effects on adipose tissue,lipoprotein lipase,and fat cell size

Adipose tissue fat cell size and lipoprotein lipase (LPL) activity were determined in the retroperitoneal and subscapular depots of nonpregnant, pregnant, and postpartum rats fed either a standard laboratory diet or a high-fat diet containing 55% fat by wieght. High-fat feeding for 20 days increased, in nonpregnant rats, fat cell size and LPL activity two-to threefold in both depots. In pregnant rats at term, fat cell size was increased and LPL activity was depressed in both dietary groups. Twenty days postpartum, both retroperitoneal fat cell size and LPL activity were decreased in proportion to the size of the litter. Rats not allowed to lactate had fat cell sizes and LPL activity that were not significantly different than in nonpregnant controls. Fat cell size and LPL activity in rats nursing four pups were reduced to 77% and 36% of control, respectively. Those nursing a normal-sized litter of eight pups demonstrated a further reduction of fat cell size to 38% and of LPL activity to 2% of nonpregnant control values. High-fat feeding and obesity did not prevent the fat loss and decreased LPL activity associated with lactation; fat cell size was decreased to 61% and LPL activity to 3% of control values. Values for the subscapular depot followed essentially the same pattern as that observed for the retroperitoneal depot. Mammary LPL activity was increased more than tenfold in animals nursing four or eight pups compared with values at term, whereas no activity was detected in rats not allowed to lactate.