Effects of a low-fat diet on levels of oxidative damage to DNA to human peripheral nucleated blood cells.

Fat in the diet has been associated with increased breast cancer risk. In this study, blood samples were obtained from 21 women at high risk for breast cancer who had been randomly assigned to either a nonintervention diet or a low-fat diet. Oxidative damage was examined in the DNA from nucleated peripheral blood cells. The levels of oxidized thymine, specifically 5-hydroxymethyluracil, were threefold higher in the nonintervention diet group than in the low-fat diet group. Without regard to diet arm, there also was a significant linear relationship between daily total fat intake and 5-hydroxymethyluracil level. These results suggest that oxidative damage to DNA may be a marker of dietary fat intake. In addition, oxidative DNA damage may be a mechanistic link between fat in the diet and cancer risk, since such damage is associated with the process of tumor promotion.

Dietary and anthropometric determinants of plasma lipoproteins during a long-term low-fat diet in healthy women.

Long-term (1 y) effects of dietary fat intake on lipoprotein metabolism were determined in 72 healthy women receiving either a 15%-fat diet (n = 34) or usual diet (n = 38). Every three months food records, weight, waist-hip ratio (W:H), percent body fat, fasting plasma triglyceride, cholesterol (C), high-density-lipoprotein cholesterol (HDL-C), HDL2-C, and HDL3-C; apolipoprotein B and A-I, and postheparin lipoprotein lipase (LPL) and hepatic triglyceride lipase activities were determined. In one year, the low-fat-diet (LFD) group had 17% and the non-intervention-diet group had 36% dietary fat. The LFD group showed decreases in cholesterol: 7% TC, 13% low-density lipoprotein (LDL), and 8% HDL. Apolipoprotein A-I, decreased early. Apolipoprotein B did not change. Plasma triglyceride correlated with weight. Percent body fat and W:H correlated with the total and LDL-C. Changes in HDL-C and/or HDL2-C and LPL correlated directly with the changes in dietary fat and inversely with dietary carbohydrate. Changes in total-C or LDL-C correlated with the changes in weight and W:H, but not with the changes in nutrient intake.

Antepartum hematocrit, maternal smoking and birth weight.

Infants born to women with hematocrit values below 31% showed an increased frequency of low birth weight. However, when the women were stratified by smoking history, differences in birth weight became apparent at the higher hematocrit levels. The data suggested an increased risk of low birth weight among women who smoke and have hematocrit values in the 41--47 range. Since smoking alters plasma volume, care should be taken when evaluating hematocrit levels measured late in pregnancy.

A randomized trial of a low-fat dietary intervention in women at high risk for breast cancer.

A randomized intervention trial of dietary fat reduction to 15% of total calories was initiated in 1987 for women at high risk for breast cancer to determine the feasibility of recruiting and maintaining them on a low-fat diet. The study has enrolled 194 women between the ages of 18 and 67 years who met at least one of three eligibility criteria: 1) a first-degree relative with breast cancer, 2) a P2 or DY Wolfe mammographic pattern, and 3) a prior breast biopsy demonstrating epithelial hyperplasia with or without atypia. Eligible women must also have had diets that contained > or = 30% of calories from fat at entry. Women were randomized to a nonintervention usual diet vs. a 15% low-fat diet. Recruitment was sought through physicians, personal mailings, breast cancer patients, and the news media. Two study sites participated: a large urban hospital affiliated with a university medical center and a community oncology private practice. The results from both institutions were similar and demonstrated that a low-fat dietary plan could be effectively conducted in private as well as academic settings with recruitment tailored to the community where the trial is being conducted. Reduction in dietary fat intake was maximal during the first three months of the dietary intervention and remained stable throughout 12 months of follow-up. Reductions in total calories, weight loss, and percent body fat were minimal. The nonintervention group experienced no major change in their diet. We conclude that it is feasible to recruit women who are at high risk for breast cancer into a dietary intervention trial and with sufficient dietary counseling and motivation on the part of participants, reduction in dietary fat intake can be achieved and maintained. More in-depth analyses of these data will be presented in subsequent reports.

C5b-7 and C5b-8 precursors of the membrane attack complex (C5b-9) are effective killers of E. coli J5 during serum incubation.

The finding that C9-deficient sera (C9D) can kill serum sensitive strains of Gram-negative bacteria by us and other investigators, questions the role of C9 in the membrane attack complex as necessary for cell death. In these studies we have demonstrated that C5b-8 complexes generated on E. coli J5 during incubation in C9-depleted and C9-neutralized sera are effective in killing Gram-negative bacteria. In the same study, we extended our investigations to show that the deposition of C5b-7 complexes (from C8-deficient [C8D], C8 depleted and C8-neutralized sera) is also effective in killing Gram-negative bacteria. In all cases, these studies demonstrated that when E. coli J5 was incubated with C8D, C9D and pooled normal human serum [PNHS], deposited C5b-9 complexes from PNHS produced more killing than C5b-7 or C5b-8 complexes alone. These experiments clearly demonstrated that C5b-7 and C5b-8 complexes are bactericidal and that multimeric C9 within C5b-9 is not an absolute requirement for inner membrane damage and cell death of Gram-negative bacteria.