|GAO, GUAN GEN|
|LUMPKIN, JR, CHARLES|
Submitted to: Toxicological Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/1/2001
Publication Date: N/A
Interpretive Summary: Lead poisoning continues to be a problem in the United States, even though much has been done to reduce child exposures. We have studied the effects of lead on bone during development and found that lead reduces bone growth and bone strength during pubertal years. Although the exact mechanisms by which lead prevents normal bone development, it was demonstrated that a particular type of bone formation (called endosteal bone) was inhibited by lead. Furthermore, hormonal treatment did not prevent or reduce these effects. The results of this study may provide the initial scientific foundation leading to ways to reverse or prevent further bone The incidence of certain cancers has traditionally been lower in populations who consumed soyfoods. The current study was conducted to determine if the incidence experimentally-induced colon cancer could be reduced by feeding rats a diet containing soy protein isolate. The data demonstrated a significant reduction in cancer of the colon in soy-fed rats, confirming the epidemiological data. This provides a basis to further study these effects by determining the mechanisms by which soy acts.
Technical Abstract: To identify possible direct and indirect mechanisms underlying the effects of lead on skeletal growth, 3 studies were conducted. In the first study, 1 male and 1 female pup/litter (n = 5 litters), were exposed ad libitum to 0, 825, or 2475 ppm lead acetate in the drinking water from gestational day 4 to euthanasia on day 55. Tibial strength was tested by 3-point bending and plasma levels of vitamin D metabolites were measured. A dose-dependent decrease of the load to failure was demonstrated but only in male pups. No differences in plasma levels of vitamin D metabolites were observed. In the second study, conducted to test if hormone treatment would attenuate the lead deficits, male and female pups were exposed to 0 or 2475 ppm lead aceetate and then, from 30-60 days of age, received either saline vehicle, L-dopa, testosterone (males only), dihydrotestosterone (DHT, males only), or estradiol (females only). Lead exposure significantly reduced somatic growth, longitudinal bone growth, and bone strength during the pubertal period. Sex steroid replacement did not restore skeletal parameters in lead-exposed rats. L-Dopa increased plasma insulin-like growth factor 1 (IGF1) concentrations, rates of bone growth, and bone strength measures in controls while having no effect in lead-exposed pups. The third study was conducted at 100 days of age, when endocrine parameters have been shown to be normalized, to test for effects of lead exposure on bone formation during tibial limb lengthening (distraction osteogenesis, DO). Both DO gap x-ray density and proximal new endosteal bone formation were decreased in the distraction gaps of the lead-treated animals (p<0.01). In conclusion, lead exposure reduced somatic growth, longitudinal bone growth, and bone strength during the pubertal period, and these effects could not be reversed by a growth hormone (GH) axis stimulator or by sex-appropriate hormones. Finally, lead exposure appears to specifically inhibit osteoblastogenesis in vivo in adult animals.