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D P Peterson

Publications and source records attributed to D P Peterson.

At least 19 recordsLinked to original sources
PubMed1997

Hepatic levels of cadmium, zinc and copper in multiparous, nulliparous and ovariectomized mice fed either a nutrient-sufficient or -deficient diet containing cadmium.

As a simulation of etiological factors known for Itai-Itai disease, female mice were subjected to the individual and combined stresses of dietary cadmium, nutrient-deficient diet, multiparity and ovariectomy. From age 68 days, female mice were maintained on either nutrient-sufficient (+) or -deficient (-), purified diets containing either 0.25 (environmental), 5, or 50 ppm Cd as CdCl(2); the nutritional composition of (-) diet simulated that of food consumed by Japanese women who contracted Itai-Itai disease. At age 70 days, half of the mice began a breeding regimen of six consecutive, 42-day rounds of pregnancy/lactation (PL mice); the remainder were maintained as virgin, non-pregnant controls (NP mice). Limited numbers of PL and NP mice were sacrificed at the end of each reproductive round. PL(+) mice taken in a given round had successively borne litters in that round and all preceding ones. PL(-) females taken at the end of round (R)-1, -2 and -3 had successively borne litters through those rounds; those taken at the end of R-5 or -6 had nonsuccessively borne litters in four of five or three of six rounds, respectively. At the end of the 252-day reproductive period, remaining females entered the 392-day, post-reproductive phase of the experiment. At age 546 days (mid-R-12), PL females having successfully borne at least three litters were ovariectomized (OV) to mimic human menopause, while NP females were either ovariectomized or sham-operated (SO). After surgery, all females were maintained to age 714 days (mid-R-16), then sacrificed. Food consumption, monitored on a weekly basis over the first nine rounds, was in general not significantly affected by dietary Cd level or nutrient deficiencies for females of the same reproductive status; consumption was increased about 2.5-fold in PL versus NP groups during the reproductive period and about 1.4-fold during the post-reproductive period. Over the reproductive period, small increases in liver concentrations of Zn and Cu were observed (ca. 3.1- and 2.5-fold, respectively) with far larger increases for Cd (ca. 22200-fold). Threshold hepatic Cd concentrations below which the concentrations of Zn and Cu were relatively constant and independent of Cd concentration were identified; they were 2.7 microg Cd/g liver for Zn and 3.3 microg Cd/g liver for Cu for females consuming (+) diet, and 4.9 microg Cd/g liver for Zn and 4.5 microg Cd/g liver for Cu for females consuming (-) diet. Regardless of Cd exposure level, round-by-round hepatic concentrations of Cd were generally 2- to 6-fold higher in PL than NP mice, while Zn or Cu levels were generally only 1.1- to 2.5-fold higher. For each reproductive round, hepatic concentrations of Cd in NP females were consistently about 10-fold greater in mice exposed to 50 than 5 ppm dietary Cd: corresponding Zn levels were essentially equivalent. For PL females. Cd levels were about 7-fold greater in 50 than 5 ppm Cd-exposed groups, however Zn concentrations were about 45% decreased. The pattern of Cd, Zn and Cu sequestration established during the reproductive period clearly differed from that of the post-reproductive period. Between R-6 and -16, hepatic concentrations of Cd, Zn and Cu appreciably decreased (14-69%) in 5 ppm Cd-exposed NPOV and PLOV females regardless of diet-type consumed. At the 50 ppm Cd level, Cd and Zn concencentrations dramatically rose with increases in Cd (37-129%) exceeding those of Zn (12-21%).

Animals↗
PubMed1997

Kidney changes in multiparous, nulliparous and ovariectomized mice fed either a nutrient-sufficient or -deficient diet containing cadmium.

As a simulation of the etiological factors known for Itai-Itai disease, a syndrome characterized by renal dysfunction and osteomalacia in its Japanese victims, female mice were subjected to the individual and combined stresses of dietary Cd, nutrient-deficient diet, multiparity and ovariectomy. Renal function as affected by the etiological factors was periodically evaluated by determination of protein, amino acid, glucose and Cd concentrations in urine; periodic changes in skeletal Ca status were assessed relative to current renal function. Renal metabolism of Cd, Zn and Cu was also examined. At age 68 days, female mice were given nutrient-sufficient (+) or -deficient (-), purified diets containing either 0.25 (environmental), 5, or 50 ppm Cd as CdCl(2); the nutritional composition of (-) diet simulated that of food consumed by Japanese victims of Itai-Itai disease. At age 70 days, half of the females began a breeding regimen of six consecutive, 42-day rounds of pregnancy/lactation (PL mice); the remainder were maintained as virgin, non-pregnant controls (NP mice). Limited numbers of PL and NP mice were sacrificed at the end of each reproductive round. PL( + ) mice taken in a given round had successively borne litters in that round and all preceding ones. PL(-) females taken at the end of round (R)-1, -2 and -3 had successively borne litters through those rounds; those taken at the end of R-5 or R-6 had nonsuccessively borne litters in four of five or three of six rounds, respectively. At the conclusion of the 252-day reproductive period, remaining females entered the 392-day, post-reproductive phase of the experiment. At age 546 days (mid-R-12), PL females having successfully borne at least three litters were ovariectomized (OV) to mimic human menopause; at the same time, NP females were either ovariectomized or sham-operated (SO). After surgery, all females were maintained to age 714 days (mid-R-16), then sacrificed. Spot urine samples were taken from individual mice at the end of most reproductive rounds (R-2-->6), prior to surgery (mid-R-10), and prior to final sacrifice (late-R-15); samples were also collected via metabolism cages at the end of R-10. Food consumption, monitored on a weekly basis over the first nine rounds, was generally not significantly affected by dietary Cd level or nutrient deficiencies in females of the same reproductive status; consumption was increased about 2.5-fold in PL versus NP groups during the reproductive period and about 1.4-fold during the post-reproductive period. At each of the three dietary Cd levels and after all reproductive rounds, mean renal Cd concentrations were 1.2- to 5.6-fold higher in PL than NP mice. After six reproductive rounds, renal Cd concentrations in PL(+) and (-) groups exposed to 50 ppm Cd had reached 155 and 179 microg Cd/g kidney, respectively. Although these levels fell within a concentration range (145-200 microg Cd/g) where cadmium-induced renal dysfunction could be anticipated, no significant, Cd-dependent changes in mean urinary amino acid or protein concentrations were found. Moreover, among the same population, a 12% incidence of elevated urinary Cd (> or = 250 ng/ml) was noted, however none of the affected individuals exhibited depressed total calcium content (TCa) or calcium:dry weight ratios (Ca:DW) for femur. Such results suggested that the Cd-induced, skeletal demineralization observed in mice during the reproductive period (Bhattacharyya et al., Toxicology 1988a; 50: 193-204; Whelton et al., Toxicology 1994: 91: 235-251) likely occurred in the general absence of cadmium-induced renal dysfunction. By the end of the post-reproductive period, the incidence of elevated urinary Cd increased to 26% among ovariectomized females: of these, 89% with urinary Cd > or = 345 ng/ml exhibited decreases in TCa and/or Ca:DW values for femur or lumbar vertebrae that exceeded one S.D. of their group mean. Such results suggested that skeletal demineralization observed at

Amino Acids↗
PubMed1997

Skeletal changes in multiparous, nulliparous and ovariectomized mice fed either a nutrient-sufficient or -deficient diet containing cadmium.

As a simulation of the etiological factors known for Itai-Itai disease, a syndrome characterized by osteomalacia and renal dysfunction in its Japanese victims, female mice were subjected to the individual and combined stresses of dietary cadmium, nutrient-deficient diet, multiparity and ovariectomy; the calcium-depleting effect of each factor was evaluated by determining Ca levels in femur and lumbar vertebrae. At age 68 days, female mice were given nutrient-sufficient (+) or -deficient (-), purified diets containing either 0.25 (environmental), 5, or 50 ppm Cd as CdCl2; the nutritional composition of (-) diet simulated that of food consumed by Japanese victims of Itai-Itai disease. At age 70 days, half of the females began a breeding regimen of six consecutive, 42-day rounds of pregnancy/lactation (PL mice); the remainder were maintained as virgin, non-pregnant controls (NP mice). Limited numbers of PL and NP mice were sacrificed at the end of each reproductive round. PL(+) mice taken at the end of round (R)-6 had successively borne litters in all six rounds, while PL(-) counterparts had nonsuccessively borne only three. At the conclusion of the 252-day reproductive period, remaining females entered the 392-day, post-reproductive phase of the experiment. At age 546 days (mid-R-12), PL females having successfully borne at least three litters were ovariectomized (OV) to mimic human menopause; at the same time, NP females were either ovariectomized or sham-operated (SO). After surgery, all females were maintained to age 714 days (mid-R-16), then sacrificed. During the post-reproductive period, food consumption by females of the same reproductive status was unaffected by elevated levels of Cd or nutrient-deficiencies in diet. However by R-16, Cd at 50 vs. 0.25 ppm had reduced body mass by 11% in both NP and PLOV females, femur and lumbar vertebral calcium content (TCa) by 20 and 25% in the respective groups, and femur and vertebral calcium/dry weight ratios (Ca/DW) by 12 and 11%. Alternative R-16 comparisons indicated that (-) diet also diminished skeletal Ca, but that the additional factors of (prior) multiparity and ovariectomy generated only small and non-significant effects. Comparison of skeletal status between the ends of the reproductive and post-reproductive periods indicated that (1) individual NP groups, regardless of Cd exposure, generally sustained small decreases in TCa and CaDW over time (consistent with aging), but PL groups without exception secured significant gains (consistent with cessation of multiparous activity), (2) skeletal integrity of PL groups was significantly more compromised by the combination of Itai etiological factors at the end of R-6 than R-16, and (3) among those factors, the most demineralizing over lifetime were chronic exposure to Cd followed by ingestion of (-) diet. Despite these findings, skeletal degeneration characteristic of the Itai-Itai syndrome was ultimately not duplicated in this mouse model suggesting that the full-blown disease required primary and profound skeletal demineralization secondarily supported and enhanced by renal dysfunction.

Animals↗
PubMed1994

Skeletal changes in multiparous and nulliparous mice fed a nutrient-deficient diet containing cadmium.

Female mice were given nutrient-deficient, purified diets containing either 0.25 (environmental), 5, or 50 ppm Cd; the nutrient quality of each was patterned after deficiencies known to be present in food consumed by Japanese women who contracted Itai-Itai disease. One-half of the mice were bred for six consecutive, 42-day rounds of pregnancy/lactation (PL mice); remaining females were non-pregnant, virgin controls (NP mice). PL and NP mice were sacrificed at the end of rounds 1, 2, 3, 5, or 6. PL mice taken during the first three rounds were successively pregnant; those taken in later rounds experienced gestation/lactation either four (round 5) or three (round 6) non-successive times. No consistent round-by-round decreases in diet consumption or body weight occurred among NP mice during the 252 days of cadmium exposure, however a significant decrease in femur calcium content (11-17%) was observed in virgin groups exposed to 50 vs. 0.25 ppm Cd. Similar femur decalcification (14-20%) was observed in PL mice, however calcium loss at 50 ppm Cd paralleled decreases in food consumption (24%) and body weight (9-17%). Significant but smaller decreases in the calcium/dry weight (Ca/DW) ratio were found for NP and PL groups consuming 50 ppm dietary Cd. Over the 6-round experiment, exposure to cadmium was found to effect smaller decreases in both femur Ca content and Ca/DW ratio than either consumption of nutrient-deficient diet or multiparous experience. Demineralization results for PL mice provide evidence that the combination of chronic ingestion of cadmium in a nutrient-deficient diet and multiparous activity likely played a role in the etiology of Itai-Itai disease; results for NP mice additionally suggest that decalcification may have been initiated in human females at a time prior to the multiparous and menopausal stages of life.

Analysis of Variance↗
PubMed1994

Scintigraphic localization of the bleeding site of a large retroperitoneal hematoma following renal angioplasty.

Although the scintigraphic detection of a few soft tissue hematomas have been reported, these usually have been serendipitous discoveries that were small and self-limited. The authors report a case of a large, rapidly expanding retroperitoneal hematoma that occurred following a left renal angioplasty. While the hematoma was initially detected by CT imaging, the precise source of the bleeding could not be definitively localized. Scintigraphy with labeled RBC cells, however, identified the left femoral artery puncture site as the bleeding source, which was subsequently surgically repaired.

Aged↗
PubMed1993

Cadmium-109 metabolism in mice. I. Organ retention in mice fed a nutritionally sufficient diet during successive rounds of gestation and lactation.

Organ retention of 109Cd was studied in multiparous and virgin female mice provided tracer amounts of 109Cd in drinking water and stable Cd appropriate for the itai-itai experience in an otherwise nutrient replete solid diet. Breeder females maximally experienced 6 consecutive, 42-d rounds of gestation/lactation. On a round-by-round basis, breeder organ 109Cd content and concentration values were compared with those from their time-matched virgin controls. By the end of round 5, the 109Cd contents of some organs appeared to have plateaued in consecutive breeders. Comparing breeder with control values at that point, the following increases were observed: whole body (minus gastrointestinal tract), 4.7-fold; mammary tissue, 14.1-fold; liver, 5.9-fold; and kidney, 3.8-fold. For 109Cd concentrations, analogous increases were mammary tissue, 15.3-fold; liver, 4.0-fold; and kidney, 2.4-fold. Through the six rounds, a temporal shift in fractional 109Cd distribution was noted for breeder tissues where transfer occurred from those of the mammaries, remaining carcass, and liver to the kidneys. In spite of this shift, at the end of round 6 109Cd content in hepatic tissue still exceeded that in renal tissue; however, 109Cd concentration was 3.3-fold greater in the kidneys. For virgin female mice over the same period, a relatively smaller shift was observed from remaining carcass to kidneys. Unlike breeders, 109Cd content was identical in hepatic and renal tissues, while 109Cd concentration was 4.6-fold greater in the kidneys. With respect to renal 109Cd increases, the larger portion of these shifts had occurred by the end of round 2 for virgin mice and by the end of round 6 for breeder mice. Comparison of content and concentration measures for a single, time-matched, virgin male group with those from a virgin female group at the end of round 6 revealed distinguishable differences only for the mammary tissues; by either measure these were about threefold higher in the female one.

Administration, Oral↗
PubMed1993

Cadmium-109 metabolism in mice. II. Organ retention in mice fed a nutritionally deficient diet during successive rounds of gestation and lactation.

Organ retention of 109Cd was studied in multiparous and virgin female mice provided trace amounts of 109Cd in drinking water and stable Cd as well as certain nutrient minerals, vitamins, and fat all apportioned in solid diet in amounts appropriate for the itai-itai experience. Breeder females maximally experienced 4 nonconsecutive rounds of gestation/lactation in a total of 5 such 42-d periods. On a round-by-round basis, breeder organ 109Cd content and concentration values were compared with those from their time-matched virgin controls. By the end of round 5, most organ 109Cd content values in breeders were still increasing. Relative to control values at that point, the following increases were observed: whole body (minus gastrointestinal tract), 4.7-fold; mammary tissue, 12.5-fold; liver, 4.7-fold; and kidney, 4.8-fold. Analogous increases in 109Cd concentration values were mammary tissue, 9.8-fold; liver, 2.8-fold; and kidney, 2.9-fold. Through the five rounds, a temporal shift in fractional Cd distribution was noted for breeder tissues where transfer occurred from those of the mammaries and remaining carcass to kidneys. Although by the end of the period 109Cd content in the liver still exceeded that in the kidneys, 109Cd concentration was 4.7-fold greater in renal tissues--an increase not matched by other breeder females consuming nutrient-replete rather than nutrient-deficient (itai-itai) diet. For virgin female mice over the same period, a shift of similar magnitude was observed from remaining carcass to kidneys. Not unlike the breeders, hepatic 109Cd content again exceeded that in renal tissues, while 109Cd concentration was 4.5-fold greater in the kidneys. With respect to renal 109Cd increases, the greater portion of these shifts had occurred by the end of round 3 for both breeder and virgin mice. Comparison of both content and concentration measures for a single, time-matched, virgin male group with those from a virgin female one at the end of round 3 showed only those for mammary tissues to be distinguishable, and by either measure were about fourfold higher in the female group.

Administration, Oral↗
PubMed1993

Cadmium-109 metabolism in mice. III. Organ retention in mice ovariectomized after experiencing multiple rounds of gestation and lactation.

Organ retention of 109Cd was studied in multiparous female mice 6 wk after ovariectomy or sham-control surgery. Females previously had experienced from three to five rounds of gestation/lactation during a maximum of 5 successive, 42-d reproductive periods. Throughout the experiment, mice were provided with tracer amounts of 109Cd in drinking water as well as stable Cd appropriate for the itai-itai experience in solid diets otherwise sufficient or deficient in nutrient quality. For sufficient-diet females, organ 109Cd content and concentration values were somewhat lower in the ovariectomized group compared to the sham control group. For deficient-diet females, the opposite trend occurred. When ovariectomized groups were compared with round 5 breeder groups of the same dietary experience, in almost all instances organ 109Cd content and concentration values were lower in the ovariectomized animals. Exceptions to this trend occurred in hepatic and especially renal tissues, where 109Cd concentrations were higher in the deficient-diet, ovariectomized group. Finally, when the deficient-diet, ovariectomized group was compared with its sufficient-diet counterpart, significantly higher 109Cd content values were found for liver, kidneys, and whole body (minus GI tract) in the former group. Conversely, when the same tissue content values were compared between the sham-control groups, differences without exception proved to be nonsignificant.

Administration, Oral↗
PubMed1992

Effects of dietary protein and salt on rat renal osmolytes: covariation in urea and GPC contents.

Renal medullary cells contain high levels of (glycine) betaine, glycerophosphorylcholine (GPC), myo-inositol, and sorbitol. Two functions of these have been proposed: 1) that they are compatible osmolytes which regulate cell volume (against high external NaCl) without inhibiting proteins and 2) that methylamines (GPC and betaine) are counteracting osmolytes which stabilize proteins against perturbation from high renal urea. As a test of the latter, osmolyte contents in kidney medullas were measured in rats subjected to three types of dietary manipulation: 1) diets with protein and NaCl contents varied oppositely, 2) diets with a constant low NaCl and varied protein content, and 3) a low-calorie diet. With low-protein and low-calorie diets, only renal contents of urea, GPC, and inositol decreased; betaine and sorbitol contents increased such that contents of total nonurea organic osmolytes remained constant. With high-protein diets, only renal contents of sodium, urea, and GPC increased, with the latter giving total organic osmolytes a consistent correlation to sodium. Across all diets, the only consistent (linear) correlations were 1) between urea and GPC contents, supporting previous suggestions that GPC is the major counteractant to urea, and 2) between total organic osmolytes and sodium (but not urea) contents, as predicted by the compatible osmolytes hypothesis.

Animals↗
PubMed1992

Cadmium-induced bone loss: increased susceptibility in female beagles after ovariectomy.

Bone resorption, as measured by release of bone 45Ca, was significantly increased in elderly female beagles within 96 h of exposure to 15 mg/l cadmium in drinking-water. The 45Ca response was greater in ovariectomized animals than in sham-operated controls and was not mediated by changes in calciotropic hormone concentrations. Mean blood cadmium concentrations were 3-8 micrograms/l during the earliest bone resorption response and 13-15 micrograms/l at the end of the study. During seven months of cadmium exposure, bone mineral densities decreased most in the ovariectomized animals exposed to cadmium: -15.4 +/- 4.3% for the tibia distal end and -7.2 +/- 1.2% for the lumbar vertebrae (L2-L4) (mean +/- SE, n = 4). The results indicate that cadmium may act directly on bone and that postmenopausal women exposed to cadmium in industry or via cigarette smoke may be at increased risk of cadmium-induced bone loss. They also support a direct role of cadmium in the etiopathology of itai-itai disease among postmenopausal women in Japan.

Animals↗
PubMed1991

Determination of cadmium in blood, plasma, and urine by electrothermal atomic absorption spectrophotometry after isolation by anion-exchange chromatography.

The determination of cadmium in whole blood, urine, or plasma by atomic absorption using electrothermal atomization is described. In preparation for atomic absorption analysis, cadmium was concentrated on an anion-exchange column, significantly lowering the limit of detection and allowing for the first time the accurate and precise determination of plasma cadmium concentrations in persons/animals with low-level cadmium exposures. Recovery of 109Cd from spiked whole blood, plasma, and urine into supernatants of nitric acid-deproteinated samples averaged 99, 100, and 95%, respectively. Anion-exchange isolation of the anionic chlorocadmium complex removed 99.8% of the major elements associated with a deproteinated whole blood sample. The recovery of 109Cd from the anion-exchange column was 92.2 +/- 0.9% (mean +/- SE, N = 35). The separation of cadmium from constituents in blood, urine, or plasma in this manner allowed comparison of unknown samples to aqueous standards with a defined acid matrix using commercially available acids. The mean intra-assay coefficient of variation (CV) was 12 +/- 3% (mean +/- SE, N = 6) for blood, plasma, and urine samples having cadmium concentrations of 0.1-0.8 microgram/liter. The interassay CV was 13% (N = 7) for a blood sample containing 0.6 microgram Cd/liter. The recovery of known amounts of cadmium added to blood, plasma, and urine in the range of 0.2 to 5.0 micrograms Cd/liter was 97 +/- 6% (mean +/- SE, N = 4).

Cadmium↗
PubMed1988

Skeletal changes in multiparous mice fed a nutrient-sufficient diet containing cadmium.

Female mice were given nutrient-sufficient, purified diets containing either 0.25, 5, or 50 ppm Cd. One-half of the females were bred for 6 consecutive 42-day rounds of pregnancy/lactation (PL mice); remaining females were non-pregnant controls (NP mice). PL mice and NP controls were sacrificed after 1, 2, 4, or 6 consecutive rounds of pregnancy/lactation. No consistent, cadmium-dependent decreases in body weight, femur calcium content, or calcium/dry weight (Ca/DW) ratio occurred among the NP mice during the 252 days of cadmium exposure. In contrast, significant, cadmium-dependent decreases in body weight (3-11%), femur calcium content (15-27%), and Ca/DW ratio (5-7%) occurred in the multiparous mice exposed to 50 vs 0.25 ppm Cd. In addition, among the PL mice, the effect of cadmium was dose-dependent, with femur calcium contents decreasing significantly as the cadmium exposure level increased from 0.25 to 5 then 50 ppm Cd (P less than 0.05). Results demonstrate that dietary cadmium exposure had a greater effect on the skeletons of dams exposed to cadmium during the stresses of pregnancy and lactation than in non-pregnant controls. The results provide evidence that the combination of cadmium exposure and multiparity may have played a role in the etiology of Itai-Itai disease in Japan.

Administration, Oral↗
PubMed1988

Kidney changes in multiparous mice fed a nutrient-sufficient diet containing cadmium.

Female mice were given nutrient-sufficient, purified diets containing cadmium at either 0.25, 5, or 50 ppm, as described in the accompanying publication. One-half of the females were bred for 6 consecutive 42-day rounds of pregnancy/lactation (PL mice); remaining females were non-pregnant controls (NP mice). PL mice and NP controls were sacrificed after 1, 2, 4, or 6 consecutive rounds of pregnancy/lactation. At all levels of dietary cadmium and after all reproductive rounds, kidney cadmium concentrations were 2-5-fold higher in PL than NP mice. After 6 rounds of reproduction, the mean concentration of cadmium in the kidneys of PL mice exposed to dietary cadmium at 50 ppm was 115 micrograms Cd/g kidney, close to the critical concentration for cadmium-induced renal damage (200 micrograms/g). No consistent increases in the concentrations of amino acids, protein, or cadmium in urine were observed in the NP or PL mice in our study, indicating that cadmium-induced renal dysfunction had not yet appeared. Very small increases in kidney concentrations of zinc and copper were observed with large increases in kidney cadmium concentrations. Threshold cadmium concentrations below which the concentrations of zinc and copper were relatively constant and independent of cadmium concentration were identified; they were 7.2 micrograms Cd/g kidney for zinc and 13 micrograms Cd/g kidney for copper. In this study, cadmium-induced decreases in bone-mineral content occurred in the PL mice exposed to cadmium at 5 and 50 ppm (see accompanying publication). Data presented here indicate that the latter bone changes occurred in the absence of cadmium-induced renal dysfunction of the type that results in increased aminoaciduria/proteinuria. They suggest that the bone disease of Itai-Ital patients may also have started prior to the onset of this type of renal dysfunction.

Administration, Oral↗
PubMed1988

Cadmium accelerates bone loss in ovariectomized mice and fetal rat limb bones in culture.

Loss of bone mineral after ovariectomy was studied in mice exposed to dietary cadmium at 0.25, 5, or 50 ppm. Results show that dietary cadmium at 50 ppm increased bone mineral loss to a significantly greater extent in ovariectomized mice than in sham-operated controls. These results were obtained from two studies, one in which skeletal calcium content was determined 6 months after ovariectomy and a second in which 45Ca release from 45Ca-prelabeled bones was measured immediately after the start of dietary cadmium exposure. Furthermore, experiments with 45Ca-prelabeled fetal rat limb bones in culture demonstrated that Cd at 10 nM in the medium, a concentration estimated to be in the plasma of mice exposed to 50 ppm dietary Cd, strikingly increased bone resorption, from 27 +/- 2% (mean +/- SEM) 45Ca release in cultures with no added cadmium to 68 +/- 6% release in cultures containing cadmium (n = 4). These in vitro results indicate that cadmium may enhance bone mineral loss by a direct action on bone. Results of the in vivo studies are consistent with a significant role of cadmium in the etiology of Itai-Itai disease among postmenopausal women in Japan and may in part explain the increased risk of postmenopausal osteoporosis among women who smoke.

Animals↗
PubMed1988

Female reproduction and pup survival and growth for mice fed a cadmium-containing purified diet through six consecutive rounds of gestation and lactation.

Female CF1 mice were bred for 6 consecutive, 42-d rounds of gestation-lactation. Their purified diets contained cadmium added at either 0.25, 5.0, or 50.0 ppm Cd; at each cadmium level, the diets were either sufficient or deficient in certain vitamins, minerals, and fat. The deficient diet at 5 ppm cadmium was designed to simulate conditions implicated in the etiology of itai-itai disease among multiparous women in Japan. Fertility, litter size, pup survival, and pup growth (weaning weight) are reported for mice on the six diets during each of the six rounds of gestation/lactation. Except for fertility, decreases in reproductive measures that occurred in response to dietary deficiencies or cadmium during round 1 of reproduction were repeated, unchanged in magnitude, in each successive round. For sufficient diet groups, 50 ppm cadmium had no effect on fertility or pup survival during lactation, but caused a 15% decrease in litter size at birth and a 25% decrease in pup growth. Dietary deficiencies alone decreased all four measures of reproductive performance: fertility by 12%, litter size by 30%, pup survival by 18%, and pup growth by 42%. In addition, dietary deficiencies strikingly decreased the incidence of consecutive pregnancies. Combined effects of 50 ppm cadmium and dietary deficiencies were additive for all reproductive measures except fertility; for fertility, cadmium caused no decrease in the fertility of sufficient-diet animals, but caused a striking 45% decrease in deficient-diet animals. Relating our results to humans, women who contracted itai-itai disease (analogous to mice on the deficient, 5 ppm cadmium diet), in addition to their characteristic bone disease, could have experienced decreases in fertility and in growth of their offspring related to their dietary deficiencies. In addition, their diet-related decreases in fertility could have been enhanced by their combined exposure to cadmium.

Animals↗
PubMed1986

Postlactational changes in cadmium retention in mice orally exposed to cadmium during pregnancy and lactation.

Mice were continuously exposed to 109Cd in drinking water (0.03 microCi/ml; 0.11 ppb total cadmium) during pregnancy and lactation. After cessation of exposure, 109Cd retention and distribution were examined during a 4-week postlactational period. At the start of the postlactational period (0 time), the fraction of oral 109Cd retained by the dams was 2.4 times greater than that retained by similarly exposed nonpregnant mice. 109Cd concentrations at 0 time were greater in the dams than in the nonpregnant mice in kidney (5-fold), liver (2.6-fold), mammary tissue (greater than 28-fold), and duodenum (13-fold). No changes in 109Cd content of the whole body (minus gastrointestinal tract) occurred during the 4 weeks after cessation of exposure in either the dams or the nonpregnant mice; i.e., pregnancy-dependent increases in 109Cd contents of individual organs were maintained during the 4 weeks of observation. An indication of translocation of 109Cd from liver to kidney was observed in the dams but not in the nonpregnant mice. 109Cd concentrations in the mammary tissue of the dams increased 2-fold during the postlactational period concomitant with a 3-fold decrease in mammary tissue mass. 109Cd in the duodenum of the pregnant/lactating mice decreased, with a half-life of 14 days. Results indicate that multiparous women exposed to environmental levels of cadmium may take up and retain in their kidneys, livers, and mammary tissue a greater fraction of their dietary cadmium than women with few or no children. Such results may bear on the etiology of Itai-Itai disease, a disease of the skeleton potentially related to oral cadmium exposure, with an incidence predominantly among postmenopausal women with a history of multiple childbirths.

Absorption↗
PubMed1985

Hematological responses to arsine exposure: quantitation of exposure response in mice.

Hematological responses of mice to arsine exposures for 1 hr at 5 to 26 part per million volume (ppmv) are described. Exposure concentrations ranged from a no-effect level for the endpoints studied (5 ppmv) to a concentration lethal to all mice in 4 days (26 ppmv). Hematocrit values at 24 hr after exposure decreased linearly with increasing arsine concentration in the range 5 to 26 ppmv; the hematocrit of the 26-ppmv group reached 10.5% at 24 hr, compared to 48.4% for control mice. Hematocrits of mice from all surviving groups were at or slightly above control values by 11 days after exposure. Changes in numbers of erythrocytes paralleled changes in hematocrit. Significant increases in circulating reticulocytes occurred at 1 and 5 days after exposure; reticulocyte values returned to control levels by 11 days after exposure. Changes in erythrocyte osmotic fragility were observed in mice exposed to 15 and 26 ppmv arsine.

Air Pollutants, Occupational↗