Nature of the enhancement of hepatic uridine diphosphate glucuronyltransferase activity by 2,3,7,8-tetrachlorodibenzo-p-dioxin in rats

Lucier, George W.; McDaniel, Otelia S.; Hook, Gary E. R.

doi:10.1016/0006-2952(75)90213-0

Cited by 91 publications

(13 citation statements)

References 19 publications

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“…Increased activity of AHH and nonsteroid UDPGT is evident postnatally, whereas steroid UDPGT was unchanged in the same animals. Differences in susceptibility to TCDD inductive actions, tissue distribution, and enzyme ontogeny have been used as criteria for the contention that steroid and nonsteroid UDPGT are at least two separate enzyme systems (10,38,39,57). UDPGT activity in extrahepatic tissues is also induced in offspring of pregnant rats administered TCDD (21).…”

Section: Modifications Of Ontogenymentioning

confidence: 99%

Metabolic activation/deactivation reactions during perinatal development.

Lucier¹,

Lui²,

Lamartiniere³

1979

Environ Health Perspect

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The role of metabolic activation/deactivation reactions during development is evaluated in relation to developmental pharmacology and toxicology. Enzyme systems evaluated include the mixed-function oxidases (aryl hydrocarbon hydroxylase and oxidative demethylation), epoxide hydration and conjugation (glutathione conjugation, sulfation, and glucuronidation). Placental transfer and milk secretion of chemicals are discussed in relation to maternal, placental, and fetal metabolism. Normal patterns of enzyme development can be modified in two ways: (1) enzyme induction and (2) enzyme imprinting. Postnatal induction of the mixed-function oxidases and glucuronyl-transferase following treatment of pregnant rats with TCDD is shown to be caused primarily by newborn exposure to TCDD in milk. Structure-activity relationship are defmed for the perinatal induction of hepatic enzymes by the pure PCBs. PCBs are divided into two classes: P-450 inducers and P-448 inducers. Imprinting or programming of hepatic metabolism is a function of the sexual differentiation of enzyme activity; male and female activities are similar in prepubertal animals, whereas pronounced sex differences are evident in adults. Treatment of newborn rats (days 2-6) with diethylstilbestrol or testosterone resulted in a feminization (decrease) of mixed-function oxidation and glucuronidation in adult males. No changes were seen in immature males or females or adult females. This effect appears to be irreversible and is under pituitary-hypothalamicgonadal control. In addition to the feminization of enzyme activity, neonatal exposure to hormonally active chemicals also feminizes the hepatic response to cadmium in resultant adult animals.

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Section: Modifications Of Ontogenymentioning

confidence: 99%

Metabolic activation/deactivation reactions during perinatal development.

Lucier¹,

Lui²,

Lamartiniere³

1979

Environ Health Perspect

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“…In Japanese Yusho patients 16 years after a similar exposure to PCBs and PCDFs, thyroid hormones including triiodothyronine (T3) and thyroxin (T4) were elevated, but (14). Secretion of thyroid-stimulating hormone (TSH) may be increased secondary to decreases of circulating T4 levels.…”

Section: Resultsmentioning

confidence: 99%

Chloracne, goiter, arthritis, and anemia after polychlorinated biphenyl poisoning: 14-year follow-Up of the Taiwan Yucheng cohort.

Guo

Yu²,

Hsu³

et al. 1999

Environ Health Perspect

101

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In 1979, a nun poisoning involving 2,000 people occrred in central Taiwan from ingestion of cooking oil contaminated by polyckorinated biphenyls (PCBs) and polyorinatd dibenaofurans (PCDFs). We studied the prevdence of medic conditions in the exposed indivduals and in a neighborhood control group. Statg with a regitry of the exposed individual from 1983, we updated the adesses of exposed individuals and identified a control group matched for age, sex, and neighborhood in 1979. In 1993, individual 30 years of age or older were interviewed by telephone. We obtained usable information from 795 eposed subjects and 693 control subjects.Lifetime prevalence of chloracne, abnormal nails, h s, skin allergy, goiter, headache, gum pigientation and broken teeth were observed more frquenty in the PCBIPCDF-eposed. men and women. The xpos men reported anemia 2.3 times more frequenty than contrls. The exposd men reported arthsitis and heriated intervertebral disks 4.1 and 2.9 times, respectively, more frequendy than controls. There was no dierence i reportd prevalences of other medical conditions. We condude that Taiwanese people exposed to high levels of PCBs and PCDFs reported more frequent medical problems, icuding skin diseas, goiter, anemia, and joint and spine diseases.

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“…Although indirect evidence supports glucuronyltransferase multiplicity, there has been a striking lack of success in separating these activities with the usual biochemical techniques. Isselbacher et al (1962) separated an N-glucuronyltransferase from an 0-glucuronyltransferase, and others have shown partial purification of glucuronyltransferases, but without definitive enzyme separation (Mowat & Arias, 1970;Lucier et al, 1975). Reports by Gorski & Kasper (1977) and by Burchell (1977) have demonstrated that a p-nitrophenol glucuronyltransferase activity can be purified to apparent homogeneity.…”

Section: Discussionmentioning

confidence: 99%

“…Since such a broad spectrum of substrates is glucuronidated, numerous studies have suggested a multiplicity of glucuronyltransferases (Dutton & Burchell, 1977). Certain examples include the lack of glucuronidation of bilirubin, but not other substrates, in the Gunn rat (Dutton, 1966), the absence of mutual product inhibition by various glucuronides (Zakim et al, 1973b), selective induction by phenobarbital, 3-methylcholanthrene and 2,3,7,8-tetrachlorodibenzop-dioxin towards glucuronidation of some substrates and not others (Sanchez & Tephly, 1973;Bock et al, 1973;Lucier et al, 1975), and changes in the various glucuronyltransferase activities in the presence of various metals (Zakim et al, 1973a). Developmental studies demonstrating a differential pattern of glucuronidation with age towards both xenobiotic and endogenous substrates (Lucier & McDaniel, 1977;Fuchs et al, 1977;Wishart et al, 1977) point toward a separate group of transferases responsible for steroid conjugation and, possibly within this group, multiple steroid glucuronyltransferase activities exist.…”

mentioning

confidence: 99%