Comparison of pQCT parameters between ulna and radius in retired elite gymnasts: the skeletal benefits associated with long-term gymnastics are bone- and site-specific.

OBJECTIVES: To compare the skeletal benefits associated with gymnastics between ulna and radius. METHODS: 19 retired artistic gymnasts, aged 18-36 years, were compared to 24 sedentary women. Bone mineral content (BMC), total and cortical bone area (ToA, CoA), trabecular and cortical volumetric density (TrD, CoD) and cortical thickness (CoTh) were measured by pQCT at the 4% and 66% forearm. RESULTS: At the 4% site, BMC and ToA were more than twice greater at the radius than ulna whereas at the 66% site, BMC, ToA, CoA, CoTh and SSIpol were 20 to 51% greater at the ulna than radius in both groups (p<0.0001). At the 4% site, the skeletal benefits in BMC of the retired gymnasts over the non-gymnasts were 1.9 times greater at the radius than ulna (p<0.001), with enlarged bone size at the distal radius only. In contrast, the skeletal benefits at the 66% site were twice greater at the ulna than radius for BMC and CoA (p<0.01). CONCLUSION: Whereas the skeletal benefits associated with long-term gymnastics were greater at the radius than ulna in the distal forearm, the reverse was found in the proximal forearm, suggesting both bones should be analysed when investigating forearm strength.

Relationship between indices of adiposity obtained by peripheral quantitative computed tomography and dual-energy X-ray absorptiometry in pre-pubertal children.

BACKGROUND/AIM: The study investigated the relationship between indices of adiposity measured by peripheral quantitative computed tomography (pQCT) and dual-energy X-ray absorptiometry (DXA) in pre-pubertal children. SUBJECTS AND METHODS: DXA-derived per cent body fat (%BF) was measured in 284 boys and 288 girls, aged 7-10 years. Cross-sections of the forearm (n=427) and lower leg (n=560) were obtained by pQCT to measure total cross-sectional area of the limb (Total CSA), Muscle CSA, Fat CSA, %Fat CSA (Fat CSA/Total CSAx100) and muscle density. RESULTS: Peripheral QCT-derived %Fat CSA in the forearm and lower leg correlated strongly with DXA-derived %BF (r=0.83-0.89, p<0.01) in both boys and girls. However, forearm and lower leg %Fat CSA were higher than whole body %BF by 5% and 10%, respectively. A better prediction of whole-body %BF was achieved by including %Fat CSA, muscle density and height into a hierarchical regression model. Using sex-specific regression equations, 87.7% of the boys and 83.7% of the girls had a predicted %BF within 3% units of the %BF obtained by DXA. CONCLUSION: In pre-pubertal children, pQCT measures of adiposity are strongly associated with whole-body per cent body fat. This reproducible method could be an alternative technique to estimate body composition in this population.

Effects of a multi-component exercise program and calcium-vitamin-D3-fortified milk on bone mineral density in older men: a randomised controlled trial.

SUMMARY: We examined the independent and combined effects of a multi-component exercise program and calcium-vitamin-D(3)-fortified milk on bone mineral density (BMD) in older men. Exercise resulted in a 1.8% net gain in femoral neck BMD, but additional calcium-vitamin D(3) did not enhance the response in this group of older well-nourished men. INTRODUCTION: This 12-month randomised controlled trial assessed whether calcium-vitamin-D(3)-fortified milk could enhance the effects of a multi-component exercise program on BMD in older men. METHODS: Men (n = 180) aged 50-79 years were randomised into: (1) exercise + fortified milk; (2) exercise; (3) fortified milk; or (4) controls. Exercise consisted of high intensity progressive resistance training with weight-bearing impact exercise. Men assigned to fortified milk consumed 400 mL/day of low fat milk providing an additional 1,000 mg/day calcium and 800 IU/day vitamin D(3). Femoral neck (FN), total hip, lumbar spine and trochanter BMD and body composition (DXA), muscle strength 25-hydroxyvitamin D and parathyroid hormone (PTH) were assessed. RESULTS: There were no exercise-by-fortified milk interactions at any skeletal site. Exercise resulted in a 1.8% net gain in FN BMD relative to no-exercise (p < 0.001); lean mass (0.6 kg, p < 0.05) and muscle strength (20-52%, p < 0.001) also increased in response to exercise. For lumbar spine BMD, there was a net 1.4-1.5% increase in all treatment groups relative to controls (all p < 0.01). There were no main effects of fortified milk at any skeletal site. CONCLUSION: A multi-component community-based exercise program was effective for increasing FN BMD in older men, but additional calcium-vitamin D(3) did not enhance the osteogenic response.

Adiposity and tendinopathy.

PURPOSE: Tendon injuries (tendinopathy) are prevalent across the population, affecting active and inactive individuals and manual workers. The aetiology of tendinopathy is not known. However, extrinsic factors such as load are known to affect the prevalence. More recently, intrinsic factors have been shown to also affect tendons; genes, biomechanics, and strength have been shown to influence tendon disease. One intrinsic factor that appears to have an association with tendinopathy is body composition; more specifically central adiposity. Several studies have reported this association, and several studies have found the association when reporting other aspects of tendinopathy. METHOD: This paper will detail what is known about the association between tendinopathy and body composition, examine the strength of the association by evaluating studies in the area and speculate on potential mechanisms for the association. RESULTS: The association between tendon health and adiposity, especially central adiposity, warrants further investigation. CONCLUSION: There may be an interaction between adiposity and tendon pathology. Adiposity may be a key intrinsic risk factor that is translated into tendon disease in the presence of additional intrinsic (e.g., diabetes) and extrinsic factors (e.g., load).

Interaction between playing golf and HRT on vertebral bone properties in post-menopausal women measured by QCT.

UNLABELLED: We investigated the effect of playing regular golf and HRT on lumbar and thoracic vertebral bone parameters (measured by QCT) in 72 post-menopausal women. The main finding of this study was that there was positive interaction between golf and HRT on vertebral body CSA and BMC at the thoracic 12 and lumbar 2 vertebra but not the third and seventh thoracic vertebras. INTRODUCTION: Identifying specific exercises that load the spine sufficiently to be osteogenic is an important component of primary osteoporosis prevention. The aim of this study was to determine if in postmenopausal women regular participation in golf resulted in greater paravertebral muscle mass and improved vertebral bone strength. METHODS: Forty-seven postmenopausal women who played golf regularly were compared to 25 controls. Bone parameters at the mid-vertebral body were determined by QCT at spinal levels T3, T7, T12 and L2 (cross-sectional area (CSA), total volumetric BMD (vBMD), trabecular vBMD of the central 50% of total CSA, BMC and cortical rim thickness). At T7 and L2, CSA of trunk muscles was determined. RESULTS: There was a positive interaction between golf and HRT for vertebral CSA and BMC at T12 and L2, but not at T3 or T7 (p ranging < 0.02 to 0.07). Current HRT use was associated with a 10-15% greater total and trabecular vBMD at all measured vertebral levels. Paravertebral muscle CSA did not differ between groups. Vertebral CSA was the bone parameter significantly related to muscle CSA. CONCLUSION: These findings provide preliminary evidence that playing golf may improve lower spine bone strength in postmenopausal women who are using HRT.

Hormone therapy is associated with smaller Achilles tendon diameter in active post-menopausal women.

The effects of hormonal status and activity levels on Achilles tendon structure were examined in asymptomatic post-menopausal women. It was hypothesized that women using hormone replacement therapy (HRT) would have better tendon structure than those not using HRT and that active women would have poorer tendon structure than inactive women. Eighty-five women including 53 active women (regular golf players) and 32 controls (healthy but inactive women) recorded their HRT and menopausal history and underwent basic anthropometric measurements. Women were divided into two groups based on their hormonal status: those currently using HRT; and those who had never used HRT or ceased using HRT at least 12 months prior to the study. Achilles tendons were examined with ultrasound and categorized as normal or abnormal, and the diameter of each tendon (mm) was recorded. Active women had a greater prevalence of tendon abnormality (P=0.10) and thicker Achilles tendons than inactive women (P<0.05). Active women on HRT had less tendon abnormality (P=0.056) than active women not on HRT and significantly less tendon thickness (P<0.05). This study indicates that Achilles tendon diameter is greater in active post-menopausal women. Hormone replacement therapy appeared to ameliorate this effect in active women. A similar effect from HRT on the Achilles tendons of inactive women was not apparent.

Lifetime sport and leisure activity participation is associated with greater bone size, quality and strength in older men.

INTRODUCTION: It remains uncertain whether long-term participation in regular weight-bearing exercise confers an advantage to bone structure and strength in old age. The aim of this study was to investigate the relationship between lifetime sport and leisure activity participation on bone material and structural properties at the axial and appendicular skeleton in older men (>50 years). METHODS: We used dual-energy X-ray absorptiometry (DXA) to assess hip, spine and ultradistal (UD) radius areal bone mineral density (aBMD) (n=161), quantitative ultrasound (QUS) to measure heel bone quality (n=161), and quantitative computed tomography (QCT) to assess volumetric BMD, bone geometry and strength at the spine (L(1)-L(3)) and mid-femur (n=111). Current (>50+ years) and past hours of sport and leisure activity participation during adolescence (13-18 years) and adulthood (19-50 years) were assessed by questionnaire. This information was used to calculate the total time (min) spent participating in sport and leisure activities and an osteogenic index (OI) score for each participant, which provides a measure of participation in weight-bearing activities. RESULTS: Regression analysis revealed that a greater lifetime (13-50+ years) and mid-adulthood (19-50 years) OI, but not total time (min), was associated with a greater mid-femur total and cortical area, cortical bone mineral content (BMC), and the polar moment of inertia (I (p)) and heel VOS (p ranging from <0.05 to <0.01). These results were independent of age, height (or femoral length) and weight (or muscle cross-sectional area). Adolescent OI scores were not found to be significant predictors of bone structure or strength. Furthermore, no significant relationships were detected with areal or volumetric BMD at any site. Subjects were then categorized into either a high (H) or low/non-impact (L) group during adolescence (13-18 years) and adulthood (19-50+ years) according to their OI scores during each of these periods. Three groups were subsequently formed to reflect weight-bearing impact categories during adolescence and then adulthood: LL, HL and HH. Compared to the LL group, mid-femur total and cortical area, cortical BMC and I (p) were 6.5-14.2% higher in the HH group. No differences were detected between the LL and HL groups. CONCLUSIONS: In conclusion, these findings indicate that long-term regular participation in sport and leisure activities categorized according to an osteogenic index [but not the total time (min) spent participating in all sport and leisure activities] was an important determinant of bone size, quality and strength, but not BMD, at loaded sites in older men. Furthermore, continued participation in weight-bearing exercise in early to mid-adulthood appears to be important for reducing the risk of low bone strength in old age.

The effect of exercise and nutrition on the mechanostat.

In this review, we discuss the effect of increased and decreased loading and nutrition deficiency on muscle and bone mass and strength (and bone length and architecture) independently and combined. Both exercise and nutrition are integral components of the mechanostat model but both have distinctly different roles. Mechanical strain imparted by muscle action is responsible for the development of the external size and shape of the bone and subsequently the bone strength. In contrast, immobilization during growth results in reduced growth in bone length and a loss of bone strength due to large losses in bone mass (a result of endosteal resorption in cortical bone and trabecular thinning) and changes in geometry (bone shafts do not develop their characteristic shape but rather develop a rounded default shape). The use of surrogate measures for peak muscle forces acting on bone (muscle strength, size, or mass) limits our ability to confirm a cause-and-effect relationship between peak muscle force acting on bone and changes in bone strength. However, the examples presented in this review support the notion that under adequate nutrition, exercise has the potential to increase peak muscle forces acting on bone and thus can lead to a proportional increase in bone strength. In contrast, nutrition alone does not influence muscle or bone in a dose-dependent manner. Muscle and bone are only influenced when there is nutritional deficiency--and in this case the effect is profound. Similar to immobilization, the immediate effect of malnutrition is a reduction in longitudinal growth. More specifically, protein and energy malnutrition results in massive bone loss due to endosteal resorption in cortical bone and trabecular thinning. Unlike loading however, there is indirect evidence that severe malnutrition when associated with menstrual dysfunction can shift the mechanostat set point upward, thus leading to less bone accrual for a given amount of bone strain.

Are unilateral and bilateral patellar tendinopathy distinguished by differences in anthropometry, body composition, or muscle strength in elite female basketball players?

BACKGROUND: Overuse injury to the patellar tendon (patellar tendinopathy) is a major reason for interrupted training and competition for elite athletes. In both sexes, the prevalence of unilateral and bilateral tendinopathy has been shown to differ. It has been proposed that bilateral pathology may have a different aetiology from unilateral pathology. Investigation of risk factors that may be unique to unilateral and bilateral patellar tendinopathy in female athletes may reveal insights into the aetiology of this condition. OBJECTIVES: To examine whether anthropometry, body composition, or muscle strength distinguished elite female basketball players with unilateral or bilateral patellar tendinopathy. METHODS: Body composition, anthropometry, and muscle strength were compared in elite female basketball players with unilateral (n = 8), bilateral (n = 7), or no (n = 24) patellar tendinopathy. Body composition was analysed using a dual energy x ray absorptiometer. Anthropometric measures were assessed using standard techniques. Knee extensor strength was measured at 180 degrees /s using an isokinetic dynamometer. z scores were calculated for the unilateral and bilateral groups (using the no tendinopathy group as controls). z scores were tested against zero. RESULTS: The tibia length to stature ratio was approximately 1.3 (1.3) SDs above zero in both the affected and non-affected legs in the unilateral group (p<0.05). The waist to hip ratio was 0.66 (0.78) SD above zero in the unilateral group (p<0.05). In the unilateral group, leg lean to total lean ratio was 0.42 (0.55) SD above zero (p<0.07), the trunk lean to total lean ratio was 0.63 (0.68) SD below zero (p<0.05), and leg fat relative to total fat was 0.47 (0.65) SD below zero (p<0.09). In the unilateral group, the leg with pathology was 0.78 (1.03) SD weaker during eccentric contractions (p<0.07). CONCLUSIONS: Unilateral patellar tendinopathy has identifiable risk factors whereas bilateral patellar tendinopathy may not. This suggests that the aetiology of these conditions may be different. However, interpretation must respect the limitation of small subject numbers.

The relationship between muscle size and bone geometry during growth and in response to exercise.

As muscles become larger and stronger during growth and in response to increased loading, bones should adapt by adding mass, size, and strength. In this unilateral model, we tested the hypothesis that (1) the relationship between muscle size and bone mass and geometry (nonplaying arm) would not change during different stages of puberty and (2) exercise would not alter the relationship between muscle and bone, that is, additional loading would result in a similar unit increment in both muscle and bone mass, bone size, and bending strength during growth. We studied 47 competitive female tennis players aged 8-17 years. Total, cortical, and medullary cross-sectional areas, muscle area, and the polar second moment of area (I(p)) were calculated in the playing and nonplaying arms using magnetic resonance imaging (MRI); BMC was assessed by DXA. Growth effects: In the nonplaying arm in pre-, peri- and post-pubertal players, muscle area was linearly associated BMC, total and cortical area, and I(p) (r = 0.56-0.81, P < 0.09 to < 0.001), independent of age. No detectable differences were found between pubertal groups for the slope of the relationship between muscle and bone traits. Post-pubertal players, however, had a higher BMC and cortical area relative to muscle area (i.e., higher intercept) than pre- and peri-pubertal players (P < 0.05 to < 0.01), independent of age; pre- and peri-pubertal players had a greater medullary area relative to muscle area than post-pubertal players (P < 0.05 to < 0.01). Exercise effects: Comparison of the side-to-side differences revealed that muscle and bone traits were 6-13% greater in the playing arm in pre-pubertal players, and did not increase with advancing maturation. In all players, the percent (and absolute) side-to-side differences in muscle area were positively correlated with the percent (and absolute) differences in BMC, total and cortical area, and I(p) (r = 0.36-0.40, P < 0.05 to < 0.001). However, the side-to-side differences in muscle area only accounted for 11.8-15.9% of the variance of the differences in bone mass, bone size, and bending strength. This suggests that other factors associated with loading distinct from muscle size itself contributed to the bones adaptive response during growth. Therefore, the unifying hypothesis that larger muscles induced by exercise led to a proportional increase in bone mass, bone size, and bending strength appears to be simplistic and denies the influence of other factors in the development of bone mass and bone shape.

The effect of mechanical loading on the size and shape of bone in pre-, peri-, and postpubertal girls: a study in tennis players.

Exercise during growth results in biologically important increases in bone mineral content (BMC). The aim of this study was to determine whether the effects of loading were site specific and depended on the maturational stage of the region. BMC and humeral dimensions were determined using DXA and magnetic resonance imaging (MRI) of the loaded and nonloaded arms in 47 competitive female tennis players aged 8-17 years. Periosteal (external) cross-sectional area (CSA), cortical area, medullary area, and the polar second moments of area (I(P), mm4) were calculated at the mid and distal sites in the loaded and nonloaded arms. BMC and I(P) of the humerus were 11-14% greater in the loaded arm than in the nonloaded arm in prepubertal players and did not increase further in peri- or postpubertal players despite longer duration of loading (both, p < 0.01). The higher BMC was the result of a 7-11% greater cortical area in the prepubertal players due to greater periosteal than medullary expansion at the midhumerus and a greater periosteal expansion alone at the distal humerus. Loading late in puberty resulted in medullary contraction. Growth and the effects of loading are region and surface specific, with periosteal apposition before puberty accounting for the increase in the bone's resistance to torsion and endocortical contraction contributing late in puberty conferring little increase in resistance to torsion. Increasing the bone's resistance to torsion is achieved by modifying bone shape and mass, not necessarily bone density.

Balancing the risk of injury to gymnasts: how effective are the counter measures?

BACKGROUND: To minimise injury risk and maximise gymnastics performance, coaches, parents, and health professionals working with young gymnasts need to understand and practise safe gymnastics. AIMS: To (a) identify the various injury counter measures specific to gymnastics, (b) critically review the literature describing each injury prevention measure, and (c) assess, using available risk factor and injury data, the weight of evidence to support each of these counter measures. Specific recommendations for further research and implementation strategies to prevent injury and improve safety are also given. METHODS: The relevant literature was identified through the use of Medline (1966 to May 1998) and SPORT Discus (1975 to May 1998) searches, hand searching of journals and reference lists, and discussions with key Australian gymnastics organisations. RESULTS: The key gymnastics injury counter measures identified in this review include coaching (physical preparation, education, spotting, and performance technique), equipment, and the health support system (medical screening, treatment, and rehabilitation). Categorisation of the type of evidence for the effectiveness of each of these counter measures in preventing injury showed that most of it is based on informal opinion/anecdotal evidence, uncontrolled data based studies, and several prospective epidemiological studies. There is no evidence from formally controlled trials or specific evaluation studies of counter measures for gymnastics. CONCLUSIONS: Although gymnastics is a sport associated with young participants and frequent high volume, high impact training, there is a paucity of information on injury risk factors and the effectiveness of injury practices. Further controlled trials are needed to examine the extent to which injury prevention counter measures can prevent or reduce the occurrence of injury and re-injury. Particular attention should be devoted to improving training facilities, the design and testing of apparatus and personal equipment used by gymnasts, and coaching and the role of spotting in preventing injury.

Short stature in competitive prepubertal and early pubertal male gymnasts: the result of selection bias or intense training?

OBJECTIVES: To determine whether high-volume, high-impact physical training in prepubertal and early pubertal male gymnasts is associated with reduced statural and segmental growth and reduced serum insulin-like growth factor-I (IGF-I) and increased cortisol (C) levels. STUDY DESIGN: Height, sitting height, leg length, and segmental lengths (humerus, radius, femur, and tibia) and breadths (biacromial and bi-iliac), diet, serum IGF-I, testosterone, and C were measured in competitive male gymnasts and normoactive children (Tanner stage < or = 2) every 3 to 4 months over an 18-month period. RESULTS: At baseline, gymnasts (n = 31) were 0.7 years older than members of the control group (P <.05, n = 50) but were no different in terms of biologic maturity. Age-adjusted z scores showed that the gymnasts were shorter than members of the control group (-0.5 +/- 0.2 SD, P <.05) because of reduced leg length (-0.8 +/- 0.2 SD, P <.001) but not sitting height. Segmental lengths and bi-iliac breadth age-adjusted z scores were also reduced in the gymnasts (P ranging <.05 to <.001). No difference was detected for serum IGF-I or C. After 18 months of follow-up, no differences were found for rates of change in height, sitting height or leg length, segmental lengths, IGF-I, or C between those gymnasts and control subjects who remained prepubertal and early pubertal (gymnasts n = 18; control group n = 35). However, the magnitudes of baseline differences in anthropometric measures (z scores) persisted throughout the study. CONCLUSION: Short stature in these competitive male gymnasts was due to a reduced leg length but not sitting height. The lack of a difference in growth rates, IGF-I, and diet over the 18-month period indicates that the short stature reported in male gymnasts is due to selection bias rather than gymnastics training.

The prepubertal years: a uniquely opportune stage of growth when the skeleton is most responsive to exercise?

The growing years may be the most opportune time in life for exercise to result in large increases in bone density, enough to reduce the risk of fracture late in life. However, it is not known if there is an 'optimal' time during growth when the skeleton is most responsive to exercise. Comparing the osteotrophic response to exercise between pre- and peripubertal children is complex because: (i) the development of the skeleton within each stage of puberty is characterised by differing temporal patterns of growth in bone size and mass; (ii) the hormonal regulation of the skeleton is unique to each stage of puberty; and (iii) it is difficult to equate the relative mechanical load placed on the prepubertal compared with the pubertal skeleton. There are sound biological bases for the hypotheses being proposed for both the pre- and peripubertal years being the time when the skeleton is most responsive to exercise; that is, exercise may enhance bone formation in a synergistic fashion in the presence of growth hormone (prepubertal years) or sex steroids (peripubertal years). The paucity of data and the complex methodology make it difficult to draw conclusions as to the most opportune time during growth when exercise may lead to the greatest osteotrophic response. The limited data available support the notion that the prepubertal years may be the most opportune time, due to increases in bone density and periosteal expansion of cortical bone.

Are Australian women sufficiently physically active to promote good mental and physical health and prevent lifestyle diseases? How can this be promoted?

Significant health benefits are associated with moderate-intensity physical activity. Only half of the women in Australia are adequately active. Strategies aimed at promoting physical activity among women should provide suitable activities and take into account the dominant barriers faced by women at different life stages.

The effects of preoperative resorption and jaw anatomy on implant success. A report of 303 cases.

The purpose of this paper is to report the outcome of 1097 consecutively implanted endosteal implants (Brånemark) into 303 jaws, between September 1983 and May 1990. All implants were placed using the prescribed technique suggested by manufacturer, and were restored either with fixed or removable prosthesis. Alveolar bone resorption (quantity) was scored from lesser to greater degree by assigning a value of 1-5 to each jaw, and jaw anatomy was scored from 1-4, based on decreasing cortical and cancellous bone quality. The data were separated into fixed and removable prosthesis and analyzed to determine the correlation between success and the scored resorption and jaw anatomy, as well as implant position. Assessment demonstrated a maxillary success rate of 93.4% and a mandibular success rate of 97.2% over a 36-month period (mean). Results of correlations of success with jaw anatomy for both fixed and removable prosthesis revealed that bone quality 4 exhibited the greatest failure rate. Preoperative resorption values (1-5) had little effect on failure, and quality appears to influence failure more than quantity.

Metabolic activation of chemical carcinogens by hepatic preparations from streptozotocin-treated rats.

The effect of insulin-dependent diabetes on the hepatic microsomal activation of chemical carcinogens to mutagenic intermediates in the Ames test was investigated in rats pretreated with streptozotocin. In order to discern between the effects of streptozotocin itself and that of the resulting diabetes, groups of streptozotocin-treated rats received either nicotinamide simultaneously with the diabetogenic agent to prevent the onset of diabetes or daily treatment with insulin in order to antagonise the effects of diabetes. The activation of two nitrosamines, nitrosopiperidine and nitrosopyrrolidine was markedly increased following treatment of the animals with streptozotocin, the effect being preventable by nicotinamide and effectively antagonised by insulin. A similar increase in mutagenic response was also seen when Glu-P-1, a carcinogen generated during the cooking of proteinaceous food, was employed as the mutagen. In contrast, the diabetic rats were less efficient than control animals in activating the aromatic amine 2-aminofluorene to mutagenic intermediates. Concomitant administration of nicotinamide with streptozotocin prevented the decrease in mutagenicity, and daily treatment of diabetic rats with insulin partially restored mutagenic response to control levels. Streptozotocin-induced diabetes had no effect on the mutagenicity of 4-aminobiphenyl and the two polycyclic aromatic hydrocarbons, benzo(a)pyrene and 3-methylcholanthrene. The present findings clearly illustrate that diabetes modulates the metabolic activation of carcinogenic chemicals, the effect being dependent on the nature of the carcinogen.

Streptozotocin-induced diabetes modulates the metabolic activation of chemical carcinogens.

The effect of chemically-induced diabetes on the hepatic microsomal mixed-function oxidase system and the activation of chemical carcinogens was investigated in animals treated with streptozotocin (STZ). In order to distinguish between the effects of the diabetogenic chemical per se and that of the diabetic state, groups of STZ-treated animals received either nicotinamide simultaneously with STZ to prevent the onset of diabetes, or daily treatment with insulin in order to reverse the effects of diabetes. STZ-treated animals exhibited higher pentoxyresorufin O-dealkylase, ethoxy-resorufin O-deethylase, ethoxycoumarin O-deethylase, aniline p-hydroxylase and NADPH-cytochrome c reductase activities; similarly, increases were seen in cytochrome P-450 and b5 levels. All of these effects were prevented by nicotinamide and, at least partly, antagonised by insulin therapy. Treatment of animals with STZ markedly increased the activation, by liver microsomes in vitro, of Trp-P-1 and Trp-P-2 to mutagens, the effect being totally preventable by nicotinamide and successfully antagonised with insulin therapy. The diabetic animals were similarly more efficient in activating MeIQ but the effect was not preventable by nicotinamide or reversed by insulin. In contrast no changes were seen in the activation of IQ and only a modest increase in the case of MeIQx. It is concluded that diabetes may modulate the metabolic activation of some chemical carcinogens, presumably by changing the ratio of the various cytochrome P-450 isoenzymes.