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Biomedical subjects

E Cho

Publications and source records attributed to E Cho.

At least 37 records · Page 2Linked to original sources
PubMed2000

Laparoscopic live donor nephrectomy: the University of Maryland 3-year experience.

PURPOSE: We determined whether laparoscopic living donor nephrectomy decreases the morbidity of renal donation for the donor, while providing a renal allograft of a quality comparable to that of open donor nephrectomy. MATERIALS AND METHODS: In a 3-year period laparoscopic donor nephrectomy was performed via the transperitoneal approach. We evaluated donor and recipient medical records for preoperative donor characteristics, intraoperative parameters and complications, and postoperative recovery and complications. RESULTS: Of the 320 laparoscopic donor nephrectomies performed the left kidney was removed in 97.5%. Intraoperative complications, which developed in 10.4% of cases, tended to occur early in the experience and required conversion to open nephrectomy in 5. Average operative time was 31/2 hours and warm ischemia time was 21/2 minutes. As the series progressed, blood loss as well as laparoscopic port size and number decreased but extraction site size remained constant at 7 cm. Urinary retention, prolonged ileus, thigh numbness and incisional hernia were the most common postoperative complications. Postoperative analgesic requirements were low and average hospitalization was 66 hours. CONCLUSIONS: Laparoscopic donor nephrectomy appears to be safe and decreases morbidity in the renal donor. Allograft function is comparable to that in open nephrectomy series. The availability of laparoscopic harvesting may be increasing the living donor volunteer pool.

Adult↗
PubMed1999

Subcellular [Ca2+]i gradients during excitation-contraction coupling in newborn rabbit ventricular myocytes.

The central role of T-tubule and sarcoplasmic reticulum (SR) diadic junctions in excitation-contraction (EC) coupling in adult (AD) ventricular myocytes suggests that their absence in newborn (NB) cells may manifest as an altered EC coupling phenotype. We used confocal microscopy to compare fluo-3 [Ca2+]i transients in the subsarcolemmal space and cell center of field-stimulated NB and AD rabbit ventricular myocytes. Peak systolic [Ca2+]i occurred sooner and was higher in the subsarcolemmal space compared with the cell center in NB myocytes. In AD myocytes, [Ca2+]i rose and declined with similar profiles at the cell center and subsarcolemmal space. Disabling the SR (10 micromol/L thapsigargin) slowed the rate of rise and decline of Ca2+ in AD myocytes but did not alter Ca2+ transient kinetics in NB myocytes. In contrast to adults, localized SR Ca2+ release events ("Ca2+ sparks") occurred predominantly at the cell periphery of NB myocytes. Immunolabeling experiments demonstrated overlapping distributions of the Na(+)-Ca2+ exchanger and ryanodine receptors (RyR2) in AD myocytes. In contrast, RyR2s were spatially separated from the sarcolemma in NB myocytes. Confocal sarcolemmal imaging of di-8-ANEPPS-treated myocytes confirmed an extensive T-tubule network in AD cells, and that T-tubules are absent in NB myocytes. A mathematical model of subcellular Ca2+ dynamics predicts that Ca2+ flux via the Na(+)-Ca2+ exchanger during an action potential can account for the subsarcolemmal Ca2+ gradients in NB myocytes. Spatial separation of sarcolemmal Ca2+ entry from SR Ca2+ release channels may minimize the role of SR Ca2+ release during normal EC coupling in NB ventricular myocytes.

Animals↗
PubMed1999

A comparison of recipient renal outcomes with laparoscopic versus open live donor nephrectomy.

BACKGROUND: Laparoscopic donor nephrectomy (laparoNx) has the potential to increase living kidney donation rates by reducing the pain and suffering of the donor. However, renal function outcomes of a large series of recipients of laparoNx have not been studied. METHODS: We retrospectively reviewed the records of 132 recipients of laparoNx done at our center between 3/96 and 11/97 and compared them to 99 recipients of kidneys procured by the open technique (openNx) done between 10/93 and 3/96. RESULTS: Significantly more patients in the laparoNx group (25.2%) were taking tacrolimus within the first month than those in the openNx group (2.1%). Mean serum creatinine was higher in laparoNx compared with openNx at 1 week (2.8+/-0.3 and 1.8+/-0.2 mg/dl, respectively; P=0.005) and at 1 month (2.0+/-0.1 and 1.6+/-0.1 mg/dl, P=0.05) after transplant. However, by 3 and 6 months, the mean serum creatinine was similar in the two groups (1.7+/-0.1 versus 1.5+/-0.05 mg/dl, and 1.7+/-0.1 versus 1.7+/-0.1, respectively). By 1 year posttransplant, the mean serum creatinine for laparoNx was actually less than that for openNx (1.4+/-0.1 and 1.7+/-0.1 mg/dl, P=0.03). Although patients in the laparoNx compared to the openNx group were more likely to have delayed graft function (7.6 versus 2.0%) and ureteral complications (4.5 versus 1.0%), the rate of other complications, as well as hospital length of stay, patient and graft survival rates were similar in the two groups. CONCLUSION: Although laparoNx allografts have slower initial function compared with openNx, there was no significant difference in longer term renal function.

Adult↗
PubMed1999

TRAF-3 mRNA splice-deletion variants encode isoforms that induce NF-kappaB activation.

Although TRAF-3 gene products are required for signaling in T-B cell collaboration, full-length TRAF-3 appears to lack signaling function in transient transfection assays that measure NF-kappaB activation. However, the TRAF-3 gene also encodes at least three mRNA splice-deletion variants that predict protein isoforms (delta25aa, delta52aa and delta56aa) with altered zinc (Zn) finger domains and unknown functional capacities. To determine whether TRAF-3 splice-deletion variants may transmit activating receptor signals to the nucleus, cDNAs for five additional splice-variant isoforms (delta27aa, delta83aa, delta103aa, delta130aa and delta221aa) were cloned from a TRAF-3+ lymphoma and the expression and function of each of the eight TRAF-3 splice-deletion variants was analyzed. Among the splice-deletion variants, TRAF-3 delta130 mRNA is expressed by tonsillar B cells and by each of a panel of B and T cell lines. TRAF-3 delta221 protein is expressed by tonsillar B cells and by each of the lymphocytic lines. The functional effect of over-expressing each TRAF-3 splice-deletion variant on NF-kappaB activation was studied in 293 T cells. Seven of the TRAF-3 splice-deletion variants, such as TRAF-3 delta130, induce substantial NF-kappaB-driven luciferase activity (80-500 fold). In contrast, TRAF-3 delta221 (in which the complete Zn finger domain is absent) fails to induce NF-kappaB activation. Although full-length TRAF-3 alone is inactive, it augments the functional effects of the seven activating TRAF-3 splice-deletion variants (1.4-5 fold). These data indicate that alterations of the Zn finger domains render the TRAF-3 splice-deletion variants capable of inducing NF-kappaB activation and that full-length TRAF-3 augments their signaling.

Alternative Splicing↗
PubMed1999

Prepubertal exposure to zearalenone or genistein reduces mammary tumorigenesis.

Prepubertal exposure to a pharmacological dose (500 mg kg(-1)) of the phyto-oestrogen genistein can reduce the incidence and multiplicity of carcinogen-induced mammary tumours in rats. However, such an exposure also disrupts the function of the hypothalamic-pituitary-gonadal axis, making it unsuitable for breast cancer prevention. We studied whether prepubertal exposure to genistein at a total body dose broadly comparable to the level typical of Oriental countries, approximately 1 mg kg(-1) body weight, affects mammary tumorigenesis. We also studied whether prepubertal exposure to zearalenone, a major source for phyto-oestrogens in the USA, influences breast cancer risk. Prepubertal rats were treated between postnatal days 7 and 20, with 20 microg (approximately 1 mg kg(-1) body weight) of either genistein or zearalenone. Zearalenone exposure significantly reduced both the incidence and multiplicity of mammary tumours induced by 7,12-dimethylbenz(a)anthracene (DMBA). Genistein exposure significantly reduced tumour multiplicity, but not tumour incidence, when compared with vehicle-treated animals. Furthermore, 60% of the tumours in the genistein group were not malignant, while all the tumours analysed for histopathology in the vehicle and zearalenone groups were adenocarcinomas. A higher number of differentiated alveolar buds, and lower number of terminal ducts, were present in the DMBA-treated mammary glands of the phyto-oestrogen exposed rats. The concentration of oestrogen receptor (ER) binding sites after the DMBA treatment was low in the mammary glands of all groups but a significantly higher proportion of the glands in the zearalenone exposed rats were ER-positive (i.e. ER levels > or = 5 fmol mg(-1) protein) than the glands of the vehicle controls. Our data suggest that a prepubertal exposure to a low dose of either zearalenone or genistein may protect the mammary gland from carcinogen-induced malignant transformation, possibly by increasing differentiation of the mammary epithelial tree.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1999

Living donor nephrectomy.

The need for more organs for kidney transplantation is increasing. Cadaver sources for these organs are stable, therefore living donation must increase if the need is to be met. Less perfect kidneys are now being transplanted. The pool of potential donors is being expanded. The process of kidney donation is being made easier in an effort to increase the number of donors. The donor work-up is being streamlined. Laparoscopic donor nephrectomy has been introduced, and appears to be promising as a technique of lessening donor pain and suffering, while maintaining excellent graft results.

Animals↗
PubMed1998

A single gene for human TRAF-3 at chromosome 14q32.3 encodes a variety of mRNA species by alternative polyadenylation, mRNA splicing and transcription initiation.

Human TRAF-3 is a signaling molecule that interacts with the cytoplasmic tails of CD40 and other TNF-receptor family members. TRAF-3 mRNA is expressed as two major classes of approximately 2 and 8 kb and a number of TRAF-3 encoding cDNA clones differ in discrete gene segments. Because this variety of mRNA species could result from mRNA processing events and/or multiple genes, the structure and localization of TRAF-3 encoding gene elements were determined. FISH and radiation hybrid mapping demonstrated that TRAF-3 is located at chromosome 14q32.3, approximately 1 Mb centromeric to the Ig heavy chain gene complex. Physical mapping of four overlapping genomic PAC clones established that TRAF-3 transcripts are encoded by a single gene, comprised of 13 exons and spanning 130 kb. Alternative polyadenylation in the mRNA segment encoded by exon 12 accounts for the difference between the 2 kb and the 8 kb classes of transcripts. Alternative mRNA splicing in the coding region (encoded by exons 3-12) generates transcripts which delete exons 8 (75 nt), 7+8 (156 nt) or 8+9 (168 nt) and that encode distinct protein isoforms (delta25, delta52 and delta56 aa, respectively). Alternative splicing of exon 2 (139 nt) and alternative transcriptional initiation result in mRNA species with distinct 5'UTRs. Together, these data indicate that a single TRAF-3 gene encodes a variety of mRNA species by a combination of alternative polyadenylation, alternative mRNA splicing and/or alternative initiation.

Alternative Splicing↗
PubMed1998

Human herpesvirus 6 reactivation is associated with cytomegalovirus infection and syndromes in kidney transplant recipients at risk for primary cytomegalovirus infection.

A potential association between human herpesvirus 6 (HHV-6) and cytomegalovirus (CMV) following kidney transplantation was explored by retrospectively testing serial serum specimens for HHV-6 IgG and IgM antibody. HHV-6 reactivation occurred in 35 (66%) of 53 transplant recipients. Fungal or parasitic opportunistic infections, graft rejection or loss, and mortality were not associated with HHV-6 reactivation. HHV-6 reactivation was associated with primary CMV infection (P=.001) and CMV syndrome (P=.003) and with trends for CMV-related hepatitis (P=.095), CMV-related neutropenia (P=.104), and serious CMV disease (P=.085). After controlling for CMV immune globulin (CMVIG) prophylaxis, the association between HHV-6 reactivation and primary CMV infection and syndrome remained significant (P=.002 and 0.006, respectively). The reduction in CMV syndrome among those receiving CMVIG prophylaxis remained significant (P=.007) after controlling for HHV-6 reactivation. HHV-6 reactivation in kidney transplant recipients at risk for primary CMV infection is associated with CMV infection and CMV-related disease, and these effects are independent of CMVIG prophylaxis.

Adult↗
PubMed1998

High maternal intake of polyunsaturated fatty acids during pregnancy in mice alters offsprings' aggressive behavior, immobility in the swim test, locomotor activity and brain protein kinase C activity.

Populations in Western countries consume an excess of polyunsaturated fatty acids (PUFA), even during pregnancy. Since (n-6) PUFA is critical for brain development, we studied whether a high maternal consumption of this fatty acid alters offsprings' affective-like behaviors and (n-6) PUFA-induced protein kinase C (PKC) activity in the brain. Three different strains of pregnant mice were fed isocaloric diets containing either 16% (control) or 43% (high) energy derived from fat high in (n-6) PUFA (corn oil: Balb/c and CD-1 mice, or soybean oil: C3H mice) throughout gestation. From birth onward dams and offspring were fed a nonpurified diet containing 12% energy from a variety of fats. Two- to 12-month-old female and male offspring of dams exposed to a high (n-6) PUFA diet during pregnancy were significantly more active in an open field, more aggressive in the resident-intruder test and spent less time immobile in the swim test than offspring of dams exposed to a control (n-6) PUFA diet. Significantly greater PKC activity in the hypothalamus and moderately less PKC activity in the whole brain (P = 0.10) were seen in the 2-month-old female and male high (n-6) PUFA offspring compared to controls. Our findings indicate that in utero exposure to a high (n-6) PUFA diet subsequently increases locomotor activity and aggression, and reduces immobility in the swim test. The mechanism mediating these effects may be linked to an increased PKC activity in the hypothalamus.

Aggression↗
PubMed1997

A maternal diet high in n - 6 polyunsaturated fats alters mammary gland development, puberty onset, and breast cancer risk among female rat offspring.

We hypothesized that feeding pregnant rats with a high-fat diet would increase both circulating 17beta-estradiol (E2) levels in the dams and the risk of developing carcinogen-induced mammary tumors among their female offspring. Pregnant rats were fed isocaloric diets containing 12% or 16% (low fat) or 43% or 46% (high fat) of calories from corn oil, which primarily contains the n - 6 polyunsaturated fatty acid (PUFA) linoleic acid, throughout pregnancy. The plasma concentrations of E2 were significantly higher in pregnant females fed a high n - 6 PUFA diet. The female offspring of these rats were fed with a laboratory chow from birth onward, and when exposed to 7,12-dimethylbenz(a)anthracene had a significantly higher mammary tumor incidence (60% vs. 30%) and shorter latency for tumor appearance (11.4 +/- 0.5 weeks vs. 14.2 +/- 0.6 weeks) than the offspring of the low-fat mothers. The high-fat offspring also had puberty onset at a younger age, and their mammary glands contained significantly higher numbers of the epithelial structures that are the targets for malignant transformation. Comparable changes in puberty onset, mammary gland morphology, and tumor incidence were observed in the offspring of rats treated daily with 20 ng of E2 during pregnancy. These data, if extrapolated to humans, may explain the link among diet, early puberty onset, mammary parenchymal patterns, and breast cancer risk, and indicate that an in utero exposure to a diet high in n - 6 PUFA and/or estrogenic stimuli may be critical for affecting breast cancer risk.

Animals↗
PubMed1997

Alterations in mammary gland development following neonatal exposure to estradiol, transforming growth factor alpha, and estrogen receptor antagonist ICI 182,780.

High fetal/early postnatal levels of estrogen increase breast cancer risk, but the mechanisms remain unknown. Growth factors, such as transforming growth factor alpha (TGF alpha), may participate as secondary modifiers in this process. We characterized a modulatory role of early postnatal exposure to 17 beta-estradiol (E2) on the developing mammary gland morphology by treating intact female CD-1 mice with physiological doses of E2 (2-4 micrograms), human recombinant TGF alpha (4 micrograms), or an estrogen receptor (ER) antagonist ICI 182,780 (20 micrograms) during postnatal days 1-3. Early postnatal exposure of E2 stimulated mammary ductal growth by days 25 and 35, but by day 50 this was inhibited. The level of differentiation from terminal end buds (TEBs) to the lobulo-alveolar units (LAUs) also was reduced by day 50. The number of TEBs was increased throughout most of the development in the female mice exposed to E2 during early life. An exposure to TGF alpha or ICI 182,780 between postnatal days 1 and 3 stimulated ductal growth, formation of TEBs, and the differentiation of mammary epithelial structures. ICI 182,80 treatment also caused hyperplastic lobular-like structures in 54-day-old females. Thus, neonatal exposure to TGF alpha and ICI 182,780 induced both similar (increase in TEBs) and different (increase/decrease in lobulo-alveolar differentiation) developmental changes in the mouse mammary gland, when compared with an exposure to E2. A unique feature of the postnatal E2 treatment was that it inhibited ductal migration by days 50-54. Our data suggest than an exposure to E2 on postnatal days 1-3, possibly combined with secondary epigenetic alterations, leads to various changes within the developing mammary tree. These changes may be potential prerequisites for mammary tumorigenesis.

Adipose Tissue↗
PubMed1997

Early postnatal treatment with transforming growth factor alpha does not alter nonreproductive behavior.

Estrogen acting during the critical developmental period has been postulated to defeminize and possibly masculinize male sexual behavior. Transforming growth factor alpha (TGF alpha) also may be involved, because this growth factor, at least partly, mediates the mitotic effects of estrogen on target tissues. Male transgenic mice overexpressing TGF alpha have elevated serum estradiol (E2) levels and they exhibit feminization of many nonreproductive actions, suggesting that either TGF alpha and/or E2, or both, participate in the control of some nonreproductive behavior. Male and female CD-1 mice were treated with 4 microg of recombinant human TGF alpha or 2-4 microg E2 during the first 3 days of life. Although early TGF alpha treatment accelerates physical development and influences the growth of the uterus and mammary gland, it failed to have any effect on behavior, either in male or female mice. Early E2 treatment significantly lengthened immobility time in the swim test and reduced voluntary alcohol intake among the male mice. No changes in locomotor activity or aggressive behavior were noted. The expression of TGF alpha mRNA in the brainstem of adult male mice was not altered following neonatal TGF alpha or E2 treatment. However, neonatal exposure to TGF alpha caused a moderate elevation in TGF alpha mRNA expression in the female brainstem. Our results indicate that in male, but not in female mice, an excess of E2 during early life affects some nonreproductive behavior. Furthermore, early treatment with recombinant human TGF alpha does not alter nonreproductive behavior in mice.

Animals↗
PubMed1997

Serum estradiol levels and ethanol-induced aggression.

The biological mechanisms behind ethanol-induced aggression are not known. Because gonadal hormones are linked both to aggression and ethanol, the present study examined relationships among the levels of serum estradiol (E2), testosterone (T), and aggressive behavior in ethanol-treated male mice. We found that among group-housed male mice, serum E2 levels were significantly elevated 30 min after a single injection of 0.6 g/kg ethanol. Serum T levels showed a nonsignificant decrease by ethanol. The E2/T ratio, an index of aromatization of T to E2, was significantly higher in the ethanol-treated animals when compared with the vehicle-treated animals. We also determined aggressive behavior in the resident-intruder test among isolated male mice at baseline (after a vehicle), and after an injection of 0.6 g/kg ethanol. The mice were grouped accordingly to those that increased, decreased, or remained nonaggressive in response to ethanol administration. We found that at baseline, neither serum T or E2 levels, nor E2/T ratio differed significantly between the increased or reduced aggressor mice. In contrast to the increase in serum E2 levels seen in the nonaggressive mice, ethanol significantly reduced circulating E2 levels, but did not affect aromatization of E2 from T in the mice that became aggressive following an ethanol injection. These data suggest that mice who exhibit a paradoxical decrease in serum E2 levels by ethanol may be particularly prone to ethanol-induced aggression.

Aggression↗
PubMed1997

Vasectomy and prostate cancer: a case-control study in India.

BACKGROUND: The role of vasectomy in the development of prostate cancer remains controversial. In particular, there has been concern about detection bias and confounding in the previously published epidemiological studies examining this hypothesis. With the goal of minimizing detection bias, we have evaluated the relation between vasectomy and prostate cancer in a population without routine prostate cancer screening. METHODS: A case-control study consisting of 175 prostate cancer cases and 978 controls with cancer diagnoses other than prostate cancer was conducted at hospitals covered by the Bombay Cancer Registry in Bombay, India. History of vasectomy, demographic, and lifestyle factors were obtained by structured interview. Multiple logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Standardizing by age, 8.7% of cases and 8.3% of controls had had a vasectomy. The OR for prostate cancer comparing men who had had a vasectomy to those who did not was 1.48 (95% CI: 0.80-2.72) controlling for age at diagnosis, smoking status, alcohol drinking, and other demographic and lifestyle factors. Risk of prostate cancer associated with vasectomy appeared to be higher among men who underwent vasectomy at least two decades prior to cancer diagnosis or who were at least 40 years old at vasectomy. CONCLUSIONS: Although not statistically significant, the results of this hospital-based case-control study are consistent with the hypothesis of a positive association between vasectomy and prostate cancer. Because routine prostate cancer screening is not common in this population, detection bias was unlikely to account for this association.

Adult↗
PubMed1997

Comparison of open and laparoscopic live donor nephrectomy.

OBJECTIVE: This study compares an initial group of patients undergoing laparoscopic live donor nephrectomy to a group of patients undergoing open donor nephrectomy to assess the efficacy, morbidity, and patient recovery after the laparoscopic technique. SUMMARY BACKGROUND DATA: Recent data have shown the technical feasibility of harvesting live renal allografts using a laparoscopic approach. However, comparison of donor recovery, morbidity, and short-term graft function to open donor nephrectomy has not been performed previously. METHODS: An initial series of patients undergoing laparoscopic live donor nephrectomy were compared to historic control subjects undergoing open donor nephrectomy. The groups were matched for age, gender, race, and comorbidity. Graft function, intraoperative variables, and clinical outcome of the two groups were compared. RESULTS: Laparoscopic donor nephrectomy was attempted in 70 patients and completed successfully in 94% of cases. Graft survival was 97% versus 98% (p = 0.6191), and immediate graft function occurred in 97% versus 100% in the laparoscopic and open groups, respectively (p = 0.4961). Blood loss, length of stay, parenteral narcotic requirements, resumption of diet, and return to normal activity were significantly less in the laparoscopic group. Mean warm ischemia time was 3 minutes after laparoscopic harvest. Morbidity was 14% in the laparoscopic group and 35% in the open group. There was no mortality in either group. CONCLUSIONS: Laparoscopic live donor nephrectomy can be performed with morbidity and mortality comparable to open donor nephrectomy, with substantial improvements in patient recovery after the laparoscopic approach. Initial graft survival and function rates are equal to those of open donor nephrectomy, but longer follow-up is necessary to confirm these observations.

Adult↗
PubMed1996

Breast cancer risk in rats fed a diet high in n-6 polyunsaturated fatty acids during pregnancy.

BACKGROUND: Women who took the synthetic estrogen diethylstilbestrol during pregnancy exhibit an elevated risk of breast cancer, whereas those who suffered from preeclampsia, which is associated with low circulating pregnancy estrogens, exhibit a reduced risk. Since a high-fat diet may increase circulating estrogen levels and possibly breast cancer risk, dietary factors during pregnancy could influence the risk of developing this disease. PURPOSE: We tested the hypothesis that consumption of a high-fat diet during pregnancy increases carcinogen-induced mammary tumor incidence in rats. METHODS: Pregnant or virgin female Sprague-Dawley rats that had been previously treated with 10 mg 7, 12-dimethylbenz[a]anthracene (DMBA) by oral gavage when 55 days old were assigned to one of two isocaloric diets containing either 16% calories from fat (low-fat) or 43% calories from fat (high-fat) for the length of pregnancy or for the equivalent time of approximately 21 days. There were 20 pregnant and 10 nonpregnant DMBA-treated rats per group. Ten additional pregnant animals (not previously treated with DMBA) per group were used for hormone analysis. The fat source used was corn oil, which is high in n-6 polyunsaturated fatty acids, primarily linoleic acid. The animals were checked for tumors at least once per week by palpation. The tumor size, number, and latency to appearance after carcinogen exposure were recorded. The statistical significance of observed differences was tested by use of appropriate two-sided tests. RESULTS: Female rats on different diets had virtually identical food intakes and weight gains during pregnancy. On gestation day 19, serum estradiol levels were approximately twofold higher in rats fed a high-fat diet than in rats fed a low-fat diet (P < .02). The serum insulin levels and insulin/glucose ratios (an index of insulin resistance) in rats fed the high-fat diet were approximately twofold lower than in rats fed the low-fat diet, but the differences did not reach statistical significance (P < .09 and P < .09, respectively). On week 18 following DMBA administration, the number of rats developing mammary tumors was significantly higher in the group exposed to a high-fat diet (40% of animals) than in the group exposed to a low-fat diet (10% of animals) during pregnancy (P < .05). Tumor multiplicity, latency to tumor appearance, and size of tumors upon first detection were similar among the dietary groups. No intergroup differences in the mammary tumor incidence were noted in virgin animals that were exposed to the high- or low-fat diets for an equivalent period of time. CONCLUSIONS: Our findings indicate that consumption of a diet high in fat (primarily in the form of n-6 polyunsaturated fatty acids) during pregnancy increases the risk of developing carcinogen-induced mammary tumors, possibly by increasing the pregnancy levels of circulating estrogens. IMPLICATIONS: If further studies find that the results from animal model studies are applicable to humans, some human breast cancers may be preventable by dietary manipulations during pregnancy.

9,10-Dimethyl-1,2-benzanthracene↗