Effects of repeated seafood consumption on urinary excretion of arsenic species by volunteers.

Arsenic (As) is a known human carcinogen and widely distributed in the environment. The main route of As exposure in the general population is through food and drinking water. Seafood harvested in Korea contains high-level organoarsenics such as arsenobetaine, arsenocholine, and arsenosugars, which are much less harmful than inorganic arsenics. However, for those who eat large amounts of seafood it is important to understand whether seafood consumption affects urinary levels of inorganic As metabolites such as arsenite, arsenate, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA). In this study we investigated urinary As metabolites (inorganic As, MMA[V], DMA[V]) and some biological indexes such as AST, GSH, GPX, lipid peroxidation, and uric acid in volunteer study subjects (seven males and nine females). Total urinary As metabolites were analyzed by the hydride generation method, followed by arsenic speciation using HPLC with ICP-mass spectrometry. Study subjects refrained from eating seafood for 3 days prior to the first urine collection and then ingested seafood daily for 6 consecutive days. The first voided urine of the morning was collected from each subject the first day of the consecutive 6 days of seafood ingestion but prior to the first seafood meal. The first voided urine of the morning was also collected on days 1, 2, 3, 4, 5, 6, 7, 10, and 14 after seafood ingestion. The daily mean intake of total As was 6.98 mg, comprised of 4.71 mg of seaweed (67%), 1.74 mg of flat fish (25%), and 0.53 mg of conch (8%). We observed a substantial increase in total urinary As metabolites for subjects consuming seafood from day 1, which recovered to control level at day 10. The increase in total urinary As metabolites was attributed to the increase in DMA, which is a more harmful metabolite than organoarsenics. However, no significant changes in response biological indexes were observed. These results suggest that it is necessary to evaluate As metabolism when assessing the exposure to inorganic As and potential chronic health effects of seafood consumption in Korea.

Toxicity Screening of Single Dose of Inorganic and Organic Arsenics on Hematological and Serum Biochemical Parameters in Male Cynomolgus Monkeys.

A screening study of the acute toxicity of organic arsenics such as arsenobetaine and arsenocholine, a product of arsenic methylation metabolite, and inorganic arsenic was carried out to examine hematological and serum biochemical parameters in cynomolgus monkeys (Macaca fascicularis). We found soft and liquid feces, and vomiting in all treated groups with inorganic and organic arsenics. The monkeys in inorganic arsenic-treated group showed a significant increase in vomiting frequency compared with those in three organic arsenics-treated groups. These results suggest that inorganic arsenic might be more toxic than three other organic arsenics tested. The monkeys in inorganic arsenic-treated group showed a decrease in platelet and an increase in monocyte on day 4 and the monkeys in arsenocholine-treated group showed an increase in reticulocyte percentage on day 8. The monkeys in inorganic-treated group also showed decreases in AST and ALT values and the monkeys in arsenobetaine-treated group showed a decrease in AST value and an increase in T-CHO value. However, these hematological and biochemical changes were within the physiological ranges, showing that the single dose of inorganic and organic arsenics did not affect at least hematological and serum biochemical parameters. The present study of toxicity with single dose of arsenics provides valuable indicators for longer term study of toxicity of repeated doses of arsenics in primates.

Synthesis of dendrimer-based biotin radiopharmaceuticals to enhance whole-body clearance.

To synthesize a biotin radiopharmaceutical that clears rapidly, dendrimer was used as a carrier and conjugated with succinimidyl 3-[(125)I]iodobenzoate and tetrafluorophenyl norbiotinamidosuccinate. Then, succinic anhydride was used to reduce its pI. In mice, the non-succinylated product showed high liver (67% ID/g) and kidney (44% ID/g) uptakes and whole-body retention (94% ID) at 20 min that persisted for 12 hr. The corresponding organ uptakes (22% and 11% ID/g) and the whole-body retention (47% ID) were drastically reduced by succinylation (p<0.0001). Lysine co-injection further lowered renal uptake.

Lowering of pI by acylation improves the renal uptake of 99mTc-labeled anti-Tac dsFv: effect of different acylating reagents.

Anti-Tac disulfide-stabilized variable region fragment (dsFv) was labeled with 99mTc by a preformed chelate approach using 99mTc-MAG3-trifluorophenyl (TFP) ester. Simultaneously it was acylated with TFP-lactate or succinic anhydride to decrease the isoelectric point of dsFv (pI 10). Acylation of dsFv (0.04 mM) with the lactate at a 73 times molar excess reduced the pI to 5.0-6.7, whereas acylation with succinic anhydride at a 30 times molar excess reduced the pI to 4.9-8.7. Comparative biodistribution studies performed in mice (n = 5) showed the reduced renal accumulation of the 99mTc proportional to the pI reduction. The effect of the pI on the reduced renal uptake was especially pronounced at 15 min postinjection. The reduced renal uptake was also reflected in the reduced whole-body retention, indicating that lowering the pI inhibited the tubular reabsorption of the labeled dsFv.