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PubMed2006

Nutritional restriction in lactating primiparous sows selectively affects female embryo survival and overall litter development.

This study explored the possibility of sex-specific effects on embryonic survival in primiparous sows subjected to restricted feed intake during the last week of lactation and bred after weaning (Restrict; n = 16), compared with control sows fed close to ad libitum feed intakes (Control; n = 17). Restrict sows were in a substantial negative net energy balance at weaning, and lost 13% of estimated protein and 17% of fat mass during lactation, yet the weaning-to-oestrous interval and ovulation rate were not different between treatments. However, embryonic survival at Day 30 of gestation was lower (P < 0.05) in Restrict than Control sows, and selectively reduced the proportion of female embryos surviving (P < 0.01). A decrease in weight and crown-rump length of surviving female (P < 0.05) and male (P < 0.05) embryos was seen in Restrict litters. The mechanisms mediating this sex-specific effect on embryonic loss in feed-restricted sows are unclear. The data presented here indicate that feed-restriction during the last week of lactation in primiparous sows causes a selective decrease in survival of female embryos and limits the growth of all surviving embryos.

Animals↗

PubMed1989

Allorecognition of DR1 by T cells from a DR4/DRw13 responder mimics self-restricted recognition of endogenous peptides.

Coculture of a series of anti-DR1Dw1 alloreactive human T-cell clones with autologous (DR4Dw4/DRw13Dw19) antigen-presenting cells and a series of recall antigens revealed that two of four clones tested proliferated in response to Candida albicans. One was restricted by DR4Dw4 and the other was restricted by DRw13Dw19. These results provide further evidence that many alloreactive T cells have a primary self-restricted specificity and cross-react on allogeneic major histocompatibility complex products. Structural comparison of the responder and stimulator DR molecules for these clones revealed that the regions predicted to contact the T cells' receptor, and thereby to determine self-restriction, are identical in sequence for DR4Dw4 and DR1Dw1 and differ by one residue between DRw13Dw19 and DR1Dw1. The DR beta residues that differ between responder, DR4Dw4 and DR13Dw19, and stimulator, DR1Dw1, are predicted to contribute to antigen binding. This implies that these anti-DR1 T cells may be specific for endogenous peptides that are bound by DR1 and not by the responder DR products, seen in a self-restricted manner. These T-cell clones also cross-reacted on DR4Dw13 and DRw14Dw16 molecules and on a human/murine hybrid class II dimer DR1 beta/I-E alpha. These reactions are discussed in terms of self-restricted peptide recognition. Thus these data suggest that in certain responder/stimulator combinations allorecognition may resemble self-restricted recognition of fragments of endogenous antigens that are bound by stimulator but not by responder major histocompatibility complex products.

Amino Acid Sequence↗

PubMed1990

Effects of food or nutrient restriction on milk vitamin A transfer and neonatal vitamin A stores in the rat.

We have investigated the effects of maternal diets low in fat or protein, or restricted in total food intake on vitamin A transfer from the dam to her pups. When animals were fed on diets moderately restricted in fat or protein, minimal differences in milk, serum, and liver vitamin A concentrations were observed compared with animals fed on a control diet. In a second study, dams were fed on diets more severely restricted in protein, or fat, or both, or were fed on a control diet equal to 50% of the intake of control rats but containing an equal amount of vitamin A. The quantity of milk obtained from these more severely restricted dams' nipples or the pups' stomachs was greatly reduced; however, there were no differences in milk vitamin A concentration. Body-weight, liver weight, and total liver vitamin A stores of undernourished pups were just half those measured for control pups, although serum vitamin A and serum retinol-binding protein were nearly normal in concentration. We conclude that (a) moderate restrictions in fat or protein in the maternal diet are insufficient to affect transfer of vitamin A to the suckling pup; (b) further dietary restrictions could cause decreased milk production with little change in milk vitamin A concentration and, hence, (c) the neonates' hepatic retinol accumulation during the suckling period is markedly reduced when maternal diets are severely deficient in fat or protein or of normal composition but restricted in amount.

Animals↗

PubMed1985

Influence of food restriction during rearing on the body composition of layer-strain pullets and hens.

The influence of two methods of food restriction during rearing on the body and liver composition of layer-type birds was investigated during and after restriction. In each of two experiments groups of birds were reared on one of three treatments: ad libitum food intake (A), time-limited food restriction (TR) or proportional food restriction (PR). All birds were fed ad libitum during the laying phase. In experiment 1, six birds from each treatment were selected at random for estimation of body and liver composition and killed at 70, 101, 162, 218 and 337 d of age. In experiment 2 four birds were selected from each treatment at 280 and 467 d of age. Body composition was predicted in experiment 2 at various times such as sexual maturity, using equations based on deuterium oxide dilution techniques. Body composition changes caused by food restriction were related to the length of restriction. Towards its end the major changes were: decreased body fat, increased total body water and increased water content of the fat-free mass for TR and PR birds compared to A birds. Some changes were not due to a reduced liveweight. Food restriction during rearing did not change body composition permanently, although predicted body fat at sexual maturity (experiment 2) was lower and protein content higher for TR and PR than for A birds. There was no demonstrable relationship between the body fat content predicted at sexual maturity and subsequent rate of lay (experiment 2).

Aging↗

PubMed1990

Effects of interactions between photostimulation, dietary restriction and dietary maize oil dilution on plasma LH and ovarian and oviduct weights in broiler breeder females during rearing.

1. The response of the reproductive system to photostimulation was investigated during the rearing period in dwarf broiler breeder females maintained from hatch on 8 h light/d. The effect of increased body fat on this response was investigated. Body fat was increased by diluting the diet with maize oil. 2. A significant increase in plasma luteinising hormone (LH) was observed 4 d after photostimulation with 20 h light/d at 3 and 15 weeks of age in birds fed the restricted diet alone and at 3, 7, 11, 15 and 19 weeks of age in birds fed the restricted diet diluted with maize oil. 3. Increases in ovarian weight were observed two weeks after photostimulation at 15 weeks of age in birds fed the restricted diet alone and at 7, 11 and 15 weeks of age in birds fed the restricted diet diluted with maize oil. Increases in oviduct weight were seen after photostimulation at 11, 15 and 19 weeks of age in both dietary treatment groups; however, a larger increase in oviduct weight was seen at 15 and 19 weeks of age in birds fed the restricted diet diluted with maize oil. 4. In a second experiment, the dilution of a diet fed ad libitum with maize oil significantly increased body fat content and the baseline concentration of LH but did not enhance the response of the reproductive system to photostimulation. 5. Baseline plasma LH concentrations were lower in birds fed ad libitum than in those fed a restricted diet. 6. It is concluded that the neuroendocrine pathways involved in the transmission of photoperiodic information are functional at 3 weeks of age. The function of the components of the hypothalamo-pituitary complex which control reproductive activity is enhanced when a restricted diet diluted with maize oil is fed.

Animals↗

PubMed1991

Response of broiler chickens and turkey poults to food restriction of varied severity during early life.

1. Cobb male (7-d-old) and female (6-d-old) chicks and BUT male and female turkeys (7-d-old), were subjected to food restriction of varying severity for 7, 5, 10 and 7d, respectively. 2. The energy allowance was calculated to support from 0% to 75% of the growth rate typical of species, strain and sex. 3. In male and female broilers kept up to 56 and 50 d, respectively, a high rate of weight gain after the restriction period (refeeding period) overcame the growth retardation attributable to restriction, except in the birds which had been subjected to the most severe regimen. In the mildest regiments, body weights reached slightly higher values than those of the ad libitum-fed controls. Overall food conversion efficiency was significantly improved in males and abdominal fat content was reduced in both sexes, regardless of the severity of restriction. 4. Body weights of male and female turkeys, aged 147 and 112 d respectively, of the groups subjected to the milder (75% growth) restriction, significantly exceeded those of the controls. Food conversion efficiency and meat yield were improved by early-age food restriction but carcase fat was not affected. 5. The results for both species of either sex suggest that a mild food restriction applied at an age of about 1 week and allowing for 60 to 75% of normal growth, may offer an economic advantage over a continuous ad libitum feeding regimen.

Animal Feed↗

PubMed2000

Diet restriction increases ubiquinone contents and inhibits progression of hepatocellular carcinoma in the rat.

BACKGROUND: The aim of the present study was to evaluate the effect of a moderate diet restriction on the progression of preneoplastic foci into hepatocellular carcinomas (HCCs) and whether such an effect was related to altered cell proliferation, apoptosis, and/or tumour contents of lipid-soluble antioxidants. METHODS: Male Wistar rats were exposed to diethylnitrosamine as initiator and 2-acetylaminofluorene plus partial hepatectomy as promoter. Six weeks after initiation the animals were given a diet restricted to 75%-80% of that given to controls until being killed 45 weeks later. Macroscopic liver tumours were histologically classified. In hepatocellular carcinomas the numbers of S-phase (labelling index) and DNA-fragmented (apoptotic index) nuclei were calculated immunohistochemically, and the tumour contents of alpha-tocopherol and ubiquinone were determined. RESULTS: The number of animals with HCC and the number of HCCs per animal were significantly reduced in restricted-diet animals compared with controls. In HCCs the contents of ubiquinone-9 and -10 were significantly increased, labelling indices were enhanced 3-fold, and apoptotic indices 12-fold as a response to food restriction. Neither the size nor the differentiation of HCCs was altered by food restriction. The numbers and areas of preneoplastic foci were similar in restricted-diet animals compared with those of controls. CONCLUSION: Moderate, long-term food restriction inhibits the progression of preneoplastic liver foci into HCC. Possible mechanisms of this inhibition are a shift in the balance between apoptosis and cell division towards cell death and an adaptive response to oxidative stress by increased tumour contents of ubiquinones.

2-Acetylaminofluorene↗

PubMed2001

Can dietary methionine restriction increase the effectiveness of chemotherapy in treatment of advanced cancer?

Most metastatic tumors, such as those originating in the prostate, lung, and gastrointestinal tract, respond poorly to conventional chemotherapy. Novel treatment strategies for advanced cancer are therefore desperately needed. Dietary restriction of the essential amino acid methionine offers promise as such a strategy, either alone or in combination with chemotherapy or other treatments. Numerous in vitro and animal studies demonstrate the effectiveness of dietary methionine restriction in inhibiting growth and eventually causing death of cancer cells. In contrast, normal host tissues are relatively resistant to methionine restriction. These preclinical observations led to a phase I clinical trial of dietary methionine restriction for adults with advanced cancer. Preliminary findings from this trial indicate that dietary methionine restriction is safe and feasible for the treatment of patients with advanced cancer. In addition, the trial has yielded some preliminary evidence of antitumor activity. One patient with hormone-independent prostate cancer experienced a 25% reduction in serum prostate-specific antigen (PSA) after 12 weeks on the diet, and a second patient with renal cell cancer experienced an objective radiographic response. The possibility that methionine restriction may act synergistically with other cancer treatments such as chemotherapy is being explored. Findings to date support further investigation of dietary methionine restriction as a novel treatment strategy for advanced cancer.

Animals↗

PubMed1980

Effects of blocking helper T cell induction in vivo with anti-Ia antibodies. Possible role of I-A/E hybrid molecules as restriction elements.

To examine the role of Ia antigens in controlling T cell activation in vivo, unprimed (CBA X B6)F1 (H-2k X H-2b) T cells were positively selected to sheep erythrocytes (SRC) for 5 d in irradiated F1 mice in the presence of large doses of anti-Iak antibody. With selection in the presence of broad-spectrum anti-Iak antibody (A.TH anti-A.TL antiserum), the activated T cells were markedly reduced in their capacity to collaborate with either B10.BR (I-Ak I-Bk I-Jk I-Ek I-Ck) (kkkkk) or B10.A(4R) (kbbbb) B cells but gave good helper responses with B10 (bbbbb) and (B10 X B10.BR)F1 B cells. Because there was no evidence for suppression, these findings were taken to imply that the anti-Iak antibody bound to Ia determinants on radioresistant macrophagelike cells of F1 host origin and blocked the activation of the IGk-restricted subgroup of F1 T cells but did not affect activation of the Iab-restricted T cell subgroup. Analogous experiments in which F1 T cells were selected to SRC in F1 mice in the presence of monoclonal anti-I-Ak antibody gave different results. In this situation, the reduction in T cell help for Iak-bearing B cells applied to B10.A(4R) B cells but not to B10.BR B cells. With selection of F1 T cells in B10.A(4R) mice, by contrast, anti-I-Ak antibody blocked T cell help for both B10.A(4R) and B10.BR B cells. These data suggested that genes telomeric to the I-A subregion were involved in controlling T cell activation and T-B collaboration. Because no evidence could be found that I-B through I-C determinants per se could act as restrictions elements, the working hypothesis for the data is that Iak-restricted T cells consist of two subgroups of cells: one subgroup is restricted by I-A-encoded molecules, whereas the other is restricted by I-A/E hybrid molecules encoded by two separated genes situated in the I-A and I-E subregions, respectively. The notion that A/E hybrid molecules serve as restriction elements is in line with the findings of other workers that these molecules can act as alloantigens and control responses to certain antigens under double Ir gene control.

Animals↗

PubMed1982

Helper T cells for cytotoxic T lymphocytes need not be I region restricted.

We investigated the antigenic requirements for restimulation of H-2- restricted cytolytic T lymphocytes (CTL) in vitro to determine whether H-2 I region-restricted helper T cells are required in these responses. In one set of experiments, we studied the in vitro response of (responder x nonresponder)F(1) female T cells to the male antigen H-Y. We chose to examine this response because it has been suggested that the defect in nonresponder strains is a failure of helper T cells to recognize H-Y in association with nonresponder I region determinants. However, we find that nonresponder male stimulator cells are as effective as F(1) male stimulator cells at inducing H-Y-specific CTL responses. This finding calls into question reports that secondary CTL responses to H-Y are dependent upon the activation of H-Y- specific helper T cells restricted to responder type I region determinants. In a second set of experiments, we examined the requirements for restimulation of H-2-restricted T cells specific for minor-histocompatibility antigens from long-term mixed lymphocyte cultures. These cultures were established by repeatedly restimulating cultures of specific T cells with H- 2-matched stimulator cells expressing foreign minor histocompatibility antigens. We found that H-2D-restricted T ceils, including CTL, could be restimulated with cells that were matched with the responding cells at only the D region genes. This response did not appear to result from positive allogeneic effects or from antigen processing and "representation" by responder type APC that might contaminate the cultures. Thus, we find no evidence for a requirement for I region-restricted helper T cells in these CTL responses. However, helper T cells are required because we find that CTL lines derived by limit-dilution cloning from these long-term MLC are absolutely dependent upon exogenous helper factors for growth. The most simple interpretation of these results is that the helper cells are restricted to H-2 antigens other than I region antigens or to antigens that code outside of the H-2 complex. Finally, we show that factor-dependent CTL lines must recognize their specific antigen to proliferate, even in the presence of exogenous factors. The requirement of activated CTL for antigen to proliferate provides an explanation for how specific CTL can be selectively enriched in MLC by specific antigen stimulation. Furthermore, it is at variance with reports that memory CTL or activated CTL require only interleukin 2 for restimulation.

Animals↗

PubMed1983

T cell regulation of b cell activation. Cloned Lyt-1+2-T suppressor cells inhibit the major histocompatibility complex-restricted interaction of T helper cells with B cells and/or accessory cells.

The present studies have identified cloned Lyt-1+2- T suppressor (Ts) cells that are both antigen specific and major histocompatibility complex (MHC) restricted in their activation requirements and that function to regulate the MHC-restricted activation of B cells by T helper (Th) cells. ParentA-restricted Ts clones suppressed, in antigen-specific fashion, the responses generated by (A X B)F1 Th cells cooperating with parentA (B plus accessory) cells, but did not suppress responses by the same (A X B)F1 Th cell population cooperating with parentB (B plus accessory) cells. Moreover, responses of (A X B)F1 leads to parentA Th cells and (A X B)F1 (B plus accessory) cells were suppressed by parentA-restricted Ts clones but not by parentB-restricted Ts clones. Thus, these findings suggest that the cloned Ts cells that have been characterized here function by specifically inhibiting the MHC-restricted interaction between Th cells and B and/or accessory cells. It was further demonstrated in experiments using cloned Th and Ts populations that these Lyt-1+2-Ts cells act not simply as inducers of suppressor but rather function in a restricted fashion as effector cells in the suppressor pathway.

Animals↗

PubMed1977

Effect of repeated food restriction-refeeding on growth rate and weight.

The effect of repeated food restriction-refeeding was investigated in male Wistar rats. After the first food restriction, rats grew faster than did ad libitum-fed animals. The extent of compensatory growth was less with each subsequent restriction-release episode. Food intake determinations gave similar results: the extent of overeating decreased with each successive restriction. Studies on the effects of the first restriction-refeeding at various sizes (ages) indicate that a considerable portion of the decrease in compensatory growth with increasing number of food restriction-refeeding is due to increasing size (age). However, some of the decreased response can be directly attributed to the repetition of food restriction.

Adaptation, Physiological↗

PubMed1984

The design of a diet restricted in saturated very long-chain fatty acids: therapeutic application in adrenoleukodystrophy.

Adrenoleukodystrophy is an inherited, progressive disorder of the CNS white matter and adrenal glands, associated with the pathognomonic accumulation of saturated very long-chain fatty acids, particularly C26:0. It has been previously demonstrated that the fatty acids that accumulate in adrenoleukodystrophy are, at least in part, of dietary origin. This observation, coupled with success of dietary phytanic acid restriction in a related disorder, Refsum's disease, encouraged us to develop a diet that would restrict dietary C26:0 intake. We report here the very long-chain fatty acids content of 135 common foods and development of a diet that restricts C26:0 intake to 3 mg, compared to 12 to 40 mg in the standard American diet. To limit C26:0 intakes it was found necessary to restrict fatty foods and the outer coverings of vegetables and fruits. In contrast to the success of phytanic acid restriction in limiting disease progress in Refsum's patients, administration of the very long-chain fatty acid-restricted diet to seven adrenoleukodystrophy patients for 3- to 24-month periods was found to be ineffective in lowering their plasma very long-chain fatty acids or in improving clinical status. Recently endogenous synthesis of C26:0 has been demonstrated and this may account for the failure of dietary therapy in adrenoleukodystrophy. It is possible that dietary restriction may augment other therapies in the future.

Adrenoleukodystrophy↗

PubMed2004

Independent and additive effects of energy restriction and exercise on glucose and insulin concentrations in sedentary overweight men.

BACKGROUND: Overweight and inactivity are associated with impaired glucose tolerance, reduced insulin sensitivity, and diabetes. Few controlled trials have assessed the independent and combined effects of energy restriction and exercise on the prevention of these conditions. OBJECTIVE: The objective was to evaluate the independent and additive effects of 16 wk of energy restriction and exercise on glucose and insulin concentrations. DESIGN: Sixty nonsmoking, overweight, sedentary men aged 20-50 y were randomly assigned to either maintain or restrict their energy intake (4186-6279 kJ/d). Within each of these arms, the subjects were further randomly assigned to either a light-intensity (control) or a vigorous-intensity exercise program for 30 min 3 times/wk. RESULTS: Fifty-one subjects completed the study. Maximal oxygen uptake increased ( approximately 24%; P < 0.001) with vigorous but not with light exercise. Significant weight loss was observed with energy restriction (x: 10.12 kg; 95% CI: 8.02, 12.22 kg; P < 0.001) but not with exercise. Vigorous exercise reduced fasting glucose and glucose and insulin areas under the curve (AUCs) by 13% (P = 0.01) and 20% (P = 0.02), respectively. Exercise effects were independent of weight change. Energy restriction resulted in a 40% reduction in the insulin AUC (P = 0.01). Vigorous exercise and energy restriction were additive in reducing the insulin AUC. CONCLUSIONS: Energy restriction and vigorous exercise independently and additively reduce glucose and insulin concentrations in response to an oral-glucose-tolerance test. Both of these lifestyle interventions provide a potent strategy that should be an integral part of any program to reduce the risk of impaired glucose tolerance, insulin resistance, and diabetes in overweight and sedentary persons.

Adult↗

PubMed1991

The effects of alternating dietary restriction and ad libitum feeding of mice on the development of diethylnitrosamine-induced liver tumours and its correlation to insulinaemia.

The effects of alternating ad libitum feeding and 30% restriction of the dietary intake on the development of diethylnitrosamine (DEN)-induced hepatic neoplasia were investigated. Dietary restriction retarded the growth of glucose-6-phosphatase-deficient (G6Pd) preneoplastic foci and subsequently that of hepatocellular adenomas and adenocarcinomas. The number of foci in standardized liver sections increased from 4.44 foci/cm2 at 12 weeks to 9.65 foci/cm2 at 24 weeks in ad libitum fed animals but only from 2.35 foci/cm2 to 3.29 foci/cm2 in restricted animals. In animals fed first ad libitum for 12 weeks and then for 12 weeks on a restricted diet, the number of G6Pd foci dropped from 4.44 at 12 weeks to 3.54 at 24 weeks. This reduction appeared to be the result of a regression of the small sized G6Pd foci. Dietary restriction was most efficient in inhibiting the development of G6Pd foci when started early in life. Conversely, the growth of foci was stimulated when the mice first had restricted access to food and thereafter were fed ad libitum. The plasma insulin concentrations after a glucose challenge increased with age. Insulinaemia was much higher in ad libitum fed compared to the restricted mice. It was correlated to the number of G6Pd foci in the liver. This study suggests that insulin, which is a known mitogen for hepatocytes in vitro, may contribute to the promotion of DEN-induced liver tumours in mice.

Adenoma↗

PubMed1996

Inhibition of 7,12-dimethylbenz[a]anthracene-induced lung tumorigenesis in A/J mice by food restriction is reversed by adrenalectomy.

Prior work has demonstrated that food restriction of mice markedly suppresses 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion of skin papillomas and adrenalectomy prior to initiating food restriction completely reverses the tumor inhibitory effect of underfeeding. In the present experiment the effect of food restriction, with or without prior adrenalectomy, on 7,12-dimethylbenz[a]anthracene (DMBA)-induced lung tumor development in A/J mice was explored. Food restriction (27%), beginning 3 weeks after a single oral dose of 0.5 mg DMBA and continued for the duration of the experiment (14 weeks), significantly inhibited lung adenoma development, whereas adrenalectomy 2 weeks before initiating food restriction abolished the tumor inhibitory effect of underfeeding and also enhanced tumor development in the ad libitum fed mice. Plasma corticosterone levels were significantly elevated in food-restricted A/J mice, whereas plasma dehydroepiandrosterone (DHEA) levels showed no apparent change. These studies suggest that adrenal gland secretory products may play a general role in the tumor preventive effect of food restriction in laboratory mice.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1997

Energy availability and mammary carcinogenesis: effects of calorie restriction and exercise.

The purpose of this experiment was to compare the carcinogenic response in the mammary gland among groups of rats whose energy metabolism had been modulated by restricting dietary calories and/or by increasing energy expenditure via exercise. Female F344 rats (n = 132) were injected i.p. with 1-methyl-1-nitrosomethylurea (50 mg/kg at 50 and 57 days of age) and were randomized into one of four treatment groups: (i) unrestricted, sedentary; (ii) calorie-restricted, sedentary; (iii) unrestricted, exercised; (iv) calorie-restricted, exercised. The targeted level of calorie-restricted was 20% and exercise was achieved by treadmill-running (20 m/min at a 15% grade for 30 min, 5 days/week). During the 20.5 week study, rats were palpated twice a week for detection of mammary tumors and urine was collected for determination of 24-h cortical steroid excretion. At the end of the study, all mammary lesions were histologically classified. Carcass composition and carcass energy were determined. Mammary carcinogenesis was inhibited among calorie-restricted, sedentary rats compared with unrestricted, sedentary rats (79% inhibition, P < 0.001). No inhibition of carcinogenesis was observed among exercised rats (unrestricted or calorie-restricted) relative to the unrestricted, sedentary rats. Within the present experimental design, exercise had no effect on carcinogenesis despite significant reductions of carcass fat and carcass energy among both groups of rats that exercised. Cortical steroid level was significantly higher only in calorie-restricted, sedentary rats (P < 0.05). These results do not support the hypothesis that reductions of body weight gain, carcass fat or carcass energy are sufficient conditions to inhibit mammary carcinogenesis. The results do suggest that changes in urinary cortical steroid excretion may predict whether an energy-related intervention is likely to alter mammary carcinogenesis.

Adrenal Cortex Hormones↗

PubMed2000

No change in spontaneous mutation frequency or specificity in dietary restricted mice.

It is well known that dietary restricted rodents live longer and are generally healthier than their ad libitum fed counterparts, with fewer tumors. Additionally, while dietary restriction appears to reduce the frequency of chemically induced mutation in laboratory animals, relatively little is known regarding the effect of dietary restriction on spontaneous mutational events. Although spontaneous mutation rates are generally low compared with chemically induced events, spontaneous mutations accumulate in most tissues over the lifetime of the animal and are therefore expected to contribute significantly to spontaneous neoplasia. It is generally presumed that dietary restriction results in less oxidative damage and a lowering of the mutation frequency. Here we report the results of dietary restriction on mutation frequency and specificity in lacI transgenic mice aged 6 and 12 months. Unexpectedly, no changes were observed in either the frequency or specificity of mutation in dietary restricted mice, compared with ad libitum controls. We therefore conclude that dietary restriction appears to have no appreciable effect on spontaneous mutation, at least in chromosomal DNA.

Age Factors↗