Biomedical subjects

Scott B Brown

Publications and source records attributed to Scott B Brown.

9 recordsLinked to original sources

PubMed2006

Biotransformation of polychlorinated biphenyls (PCBs) and bioformation of hydroxylated PCBs in fish.

Hydroxylated PCBs (OH-PCBs) are a class of organic contaminants that have been found recently in the plasma of Great Lakes fish, the source of which is either bioformation from PCBs or accumulation from the environment. To address the potential for fish to biotransform PCBs and bioform OH-PCBs juvenile rainbow trout (Oncorhynchus mykiss; approximately 80 g) were exposed to dietary concentrations of an environmentally relevant mixture of PCBs. Eight OH-PCBs were found in the plasma of rainbow trout after 30 days of exposure to the PCBs, the relative pattern of which was similar to those observed in wild lake trout (Salvelinus namaycush) from Lake Ontario. Hydroxylated-PCBs were not found (detection limit 0.02 pg/g) in the food or control (not PCB-exposed) fish. A curvilinear logt(1/2)-logK(ow) relationship for recalcitrant PCBs was found, similar to previously reported relationships, although t(1/2) values were longer and shorter than studies using smaller fish or cooler temperatures, respectively. A number of PCB congeners fell below the logt(1/2)-logK(ow) relationship providing the first estimates of non-chiral PCB biotransformation rates in fish. Enantioselective degradation of the chiral congeners PCBs 91 and 136, also indicated biotransformation. Biotransformation of PCBs was structure-dependent with greater biotransformation of PCBs with vicinal hydrogen atoms in the meta/para positions, suggesting CYP 2B-like biotransformation. Other chiral congeners with a meta/para substitution pattern showed no enantioselective degradation but were biotransformed based on the logt(1/2)-logK(ow) relationship. The results of this study demonstrate that laboratory held rainbow trout can biotransform a number of PCB congeners and that bioformation is likely an important source of OH-PCBs in wild salmonids of the Great Lakes.

Animals↗

PubMed2005

Development of a short-term in situ caging methodology to assess long-term effects of industrial and municipal discharges on salmon smolts.

Trial experiments to develop an in situ method for determining effects of short-term exposure to contaminants on salmon during the sensitive smolt stage were carried out. Wild Atlantic salmon (Salmo salar) smolts were caged at various estuarine locations in northeast New Brunswick, Canada at different levels of anthropogenic impact in 2000 and 2001. Survival, growth (weight and K), and feeding (delta(13)C and delta(15)N) parameters were measured following summer grow-out at a hatchery. A summary of distributions of the four parameters indicated that smolts caged at locations receiving lower levels of industrial and municipal discharges feed and grow better than those caged at sites receiving higher levels. The findings, however, were not repeatable between the 2 years studied. The observed inconsistency between years may be a consequence of the relatively low concentrations of alkylphenolic contaminants (putative causative agents) and overall steroidogenic potency in river water at the time of caging. Differences in temperature and salinity from 2000 to 2001 may have further confounded comparisons across treatments and between years. In future studies, caging in closer proximity to industrial and municipal discharges or in systems with higher concentrations of waterborne contaminants or impoundments would help further the assessment and applicability of this methodology and allow a more robust comparison of smolt feeding and growth among reference and exposure sites.

Animals↗

PubMed2005

Effects of maternally transferred organochlorine contaminants on early life survival in a freshwater fish.

Laboratory research has shown that female fish can pass toxic organochlorines (OCs) from their bodies to their eggs, killing their offspring if sufficient quantities are transferred. We conducted a controlled incubation study using gametes from a wild, OC-contaminated walleye (Sander vitreus) population (Bay of Quinte, Lake Ontario, Canada) in order to assess among-female variation in offspring early life survival in relation to ova concentrations of planar OCs (polychlorinated dibenzo-p-dioxins and furans and planar polychlorinated biphenyls) and a suite of other maternal and ova characteristics. Equal volumes of ova from each female were fertilized, pooled, and incubated together as an experimental cohort. Relative survival of each female's offspring was estimated as the proportion of surviving larvae (at approximately 5 d posthatch) that she contributed to the cohort as determined by microsatellite DNA parentage assignment. Total planar OC concentration (expressed as toxic equivalency of 2,3,7,8-tetrachlorodibenzo-p-dioxin) of ova was positively related to maternal age and size and to ova lipid content. However, early life survival did not decline with increasing ova planar OC concentrations. Similarly, we observed no significant relationships between early life survival and ova thiamine content, ova fatty acid composition, or maternal age or size. Early life survival was more strongly correlated with date of spawn collection, thyroid hormone status of the ova, and ovum size. Maternally transferred planar OCs do not appear to negatively influence female reproductive success in this walleye population.

Animals↗

PubMed2004

Dietary retinoic acid induces hindlimb and eye deformities in Xenopus laevis.

This study investigated the effects of dietary retinoic acid (RA) on frog hindlimb development. Xenopus laevis (African clawed frog) tadpoles were fed a diet supplemented with 0, 1, 10, or 100 microg of RA/g of food for 2 or 5 d at different stages of metamorphosis. Hindlimb deformities were induced in the group fed 100 microg of RA/g of diet for 5 d. Exposures beginning at mid-hindlimb bud development induced bilaterally bent tibiafibula (bony triangles), while exposures later in hindlimb development induced deformities of the feet, including fusion of the 1st and 2nd clawed digits and reduced length of the 4th and 5th digits (due to reduced, missing, or misplaced phalanges). There were also cases of extra phalanges in the 5th digit. The eye was another target of RA exposure. In one experiment, 58% of the tadpoles fed 10 microg of RA/g had a smaller or absent right eye. Additionally, 11% of the tadpoles fed 100 microg of RA/g of diet developed a smaller or absent left eye. Waterborne heavy metals (Zn or Cu) modified RA effects on the hindlimb and eye. Co-exposure to metals and RA resulted in cases of unilateral bony triangles and reduced rates of smaller eyes. There were also cases of extra hindlimb digits in Zn-exposed animals. Dietary RA exposure in tadpoles can cause some deformities that differ from waterborne RA exposures in previous studies. RA also induced deformities that resemble those in affected wild frog populations (bony triangles), although the patterns of other deformities and missing segments (phalanges and metatarsals) are not similar to those documented in the wild.

Abnormalities, Drug-Induced↗

PubMed2004

Altered thyroid status in lake trout (Salvelinus namaycush) exposed to co-planar 3,3',4,4',5-pentachlorobiphenyl.

Recent studies indicate that co-planar 3,3',4,4',5-pentachlorobiphenyl (PCB) congeners or their metabolites may disrupt thyroid function in fishes. Although co-planar PCB have been detected at microgram per kilogram levels in fish from contaminated areas, few studies have examined mechanisms whereby, co-planar PCBs may alter thyroid function in fish. We treated immature lake trout by intraperitoneal (i.p.)-injection or dietary gavage with vehicle containing 0, 0.7, 1.2, 25 or 40 microg 3,3',4,4',5-pentachlorobiphenyl (PCB 126) per kgBW. Blood and tissue samples were collected at various times up to 61 weeks following exposure. The treatments produced sustained dose-dependent elevations of tissue (PCB 126) concentrations. Thyroid epithelial cell height (TECH), plasma thyroxine (T4) and 3,3',5-triiodo-l-thyronine (T3) concentrations, hepatic 5'-monodeiodinase, hepatic glucuronidation of T4 and T3, as well as plasma T4 kinetics and fish growth were analyzed. Exposure to the highest doses of PCB 126 caused increased TECH, plasma T4 dynamics and T4-glucuronidation (T4-G). PCB 126 did not affect 5'-monodeiodinase and T3-glucuronidation (T3-G) and there were no effects on fish growth or condition. Because T3 status and growth were unaffected, the thyroid system was able to compensate for the alterations caused by the PCB 126 exposure. It is clear that concentrations of co-planar PCBs similar to those found in predatory fish from contaminated areas in the Great Lakes are capable of enhancing metabolism of T4. These changes may be of significance when T4 requirements are high for other reasons (e.g. periods of rapid growth, warm temperatures, metamorphosis, and parr-smolt transformation).

Analysis of Variance↗

PubMed2004

Contaminant effects on the teleost fish thyroid.

Numerous environmentally relevant chemicals, including polychlorinated hydrocarbons, polycyclic aromatic hydrocarbons, organochlorine pesticides, chlorinated paraffins, organophosphorous pesticides, carbamate pesticides, cyanide compounds, methyl bromide, phenols, ammonia, metals, acid loads, sex steroids, and pharmaceuticals, exert acute or chronic effects on the thyroid cascade in the approximately 40 teleost fish species tested to date. Thyroid endpoints, therefore, serve as biomarkers of exposure to environmental pollutants. However, the mechanisms underlying thyroid changes and their physiological consequences are poorly understood because the thyroid cascade may respond indirectly and it has considerable capacity to compensate for abuses that otherwise would disrupt thyroid hormone homeostasis. Indeed, a xenobiotic-induced change in fish thyroid function has yet to be conclusively causally linked to decreased fitness or survival. Other complications in interpretation arise from the diversity of test conditions employed and the often indiscriminate use of numerous thyroid endpoints. Future work should be directed toward standardizing test conditions and thyroid endpoints and investigating causal links between thyroid changes and fish growth, reproduction, and development. Development may be particularly susceptible to thyroid disruption, and thyroid endpoints appropriate for early life stages need to be applied.

Animals↗

PubMed2004

Toxicokinetics of three polychlorinated biphenyl technical mixtures in rainbow trout (Oncorhynchus mykiss).

Accumulation and depuration parameters of polychlorinated biphenyls (PCBs) in fish have been reported only for a few congeners. As well, there is little information on the ability of fish to biotransform PCBs. To address these issues, juvenile rainbow trout (Oncorhynchus mykiss) were exposed to dietary concentrations of three Aroclor mixtures (1248, 1254, 1260) in food for 30 d followed by an additional 160 d of nonspiked food at 8 degrees C. Accumulation, depuration, and potential biotransformation of 92 PCB congeners were assessed. Half-lives (t1/2) of PCB congeners ranged from 79 to 182 d, assimilation efficiencies ranged from 40 to 50% and biomagnification factors (BMF) ranged from 2.9 to 6.9. No evidence of significant biotransformation of any PCB congeners was found. All 92 congeners fell on the same t1/2 to Kow relationship as 16 preselected PCB congeners previously shown to persist in fish and no hydroxylated PCB metabolites (OH-PCBs) were detected in the plasma after 30 d of exposure. These findings suggest that OH-PCBs observed in feral fish may be accumulated from sources other than internal metabolism of the parent congeners, at least for juvenile fish at cool temperatures. Because t1/2s in this experiment were slower than t1/2s reported in other work, water temperature also may be an important factor in determining the t1/2s of all PCB congeners in fish.

Animals↗

PubMed2003

Association of cocaine withdrawal symptoms with more severe dependence and enhanced subjective response to cocaine.

The purpose of this two part study was to better characterize cocaine users based on self-reported cocaine withdrawal symptoms by examining screening data and response to smoked cocaine in the human laboratory. The first study sample included male and female non-treatment seeking cocaine users who were screened as potential subjects for inpatient studies. Of the 555 subjects, 462 (82%) endorsed symptoms consistent with DSM-IV criteria for cocaine withdrawal. Cocaine users who met criteria for cocaine withdrawal, compared with those who did not, reported a significantly higher amount of cocaine use and a history of medical and psychosocial problems. Cocaine users meeting DSM-IV withdrawal criteria, which included endorsement of depression, were also more likely to have a history of depression, to have seriously considered suicide, and to have had chemical dependency treatment even when amount spent on cocaine was covaried. The second study sample, which was a subset of Study I, included those who participated in human cocaine studies following the phone screening. Cocaine users who met criteria for cocaine withdrawal (n=34), compared with those who did not (n=10), had enhanced subjective ratings of 'high' and 'feel the effect of last dose' in response to a single delivery of 0.4 mg/kg of smoked cocaine. These results suggest that history of cocaine withdrawal symptoms may be associated with enhanced cocaine responses and greater severity of cocaine dependence.

Adult↗

PubMed2002

Dietary accumulation and biochemical responses of juvenile rainbow trout (Oncorhynchus mykiss) to 3,3',4,4',5-pentachlorobiphenyl (PCB 126).

Juvenile rainbow trout (Oncorhynchus mykiss) (initial weights 2-5 g) were exposed to three dietary concentrations (0, 12.4 and 126 ng g(-1), wet weight) of a 14C-labelled 3,3',4,4',5-pentachlorobiphenyl (PCB 126) for 30 days followed by 160 days of clean food. We assessed bioaccumulation, histology (liver and thyroid) and biochemical responses (liver ethoxyresorufin-O-deethylase (EROD), liver vitamins (retinoids and tocopherol) and muscle thyroid hormone levels) along with growth and survival. The half-life of PCB 126 in the rainbow trout ranged from 82 to 180 days while biomagnification factors (BMF) ranged from 2.5 to 4.1 providing further evidence that PCB 126 is among the most bioaccumulative PCB congeners. Toluene extractable 14C declined with time in the trout suggesting the possibility of some biotransformation and/or covalent bonding with biological macromolecules. The threshold for liver EROD induction by PCB 126 was approximately 0.1 ng g(-1) (wet weight). EROD activities in the low- and high treatments were 9 and 44 times greater than control, respectively, and remained elevated throughout the experiment. EROD activity was correlated with whole body concentrations of PCB 126 although there was evidence of EROD activity suppression in the highly exposed fish. Liver didehydroretinoids and tocopherol concentrations were depressed by the high PCB 126 dose after 30 days exposure. Initially, muscle concentrations of thyroxine (T4) and triiodo-L-thyronine (T3) declined as the fish grew during the experiment, and exposure to PCB 126 accelerated the growth related decline. More information is needed to assess the functional significance of the reduced muscular stores of thyroid hormones. Despite the changes in liver EROD, liver vitamins and muscle thyroid hormones, liver and thyroid histology in trout examined after 30 days exposure and growth parameters were unaffected by PCB 126. This indicates that the functional competences of the physiological factors associated with growth were maintained under the experimental conditions.

Animals↗