1967
DOI: 10.3181/00379727-125-32086
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Species Variations in the N - and Ring-Hydroxylation of 2-Acetylaminofluorene and Effects of 3-Methylcholanthrene Pretreatment.

Abstract: Rats treated with the carcinogen 2-acetylaminofluorene ( AAF) excrete major fractions of the administered compound in the urine as the N-, 3-, 5-, and 7-hydroxy derivatives ( 1-3) and in the bile as N-hydroxy-AAF( 4). The liver endoplasmic reticulum is a major site of the enzyme systems which perform these hydroxylations, all of which require T P N H and oxygen(5-7). The activity of the hepatic aromatic ring-hydroxylases increases approximately 1 0-fold when weanling rats are treated 24 hours prior to assay wi… Show more

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Cited by 70 publications
(25 citation statements)
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“…On the other hand, cytochrome P-450 dependent C-hydroxylations (Lotlikar et al, 1967) and cytochrome P-450 dependent reduction of the N-hydroxylated metabolite back to the parent compound (Yamazoe et al, 1980), represent important detoxifying steps. Obviously, the resultant effect of inhibitors of cytochrome P-450 may often be difficult to predict.…”
Section: Discussionmentioning
confidence: 99%
“…On the other hand, cytochrome P-450 dependent C-hydroxylations (Lotlikar et al, 1967) and cytochrome P-450 dependent reduction of the N-hydroxylated metabolite back to the parent compound (Yamazoe et al, 1980), represent important detoxifying steps. Obviously, the resultant effect of inhibitors of cytochrome P-450 may often be difficult to predict.…”
Section: Discussionmentioning
confidence: 99%
“…Whereas N-hydroxy derivatives of certain monocyclic N-arylacetamides, such as 4-C1AA and PH were found in very low amounts only in incubates of liver microsomes from rabbits (41,43), hamsters (40,42), and mice (44), and in the urine of hamsters (46), and rats (47),larger amounts of the N-hydroxy derivatives of the polycyclic N-arylacetamides 4-AAB and 2-AAF were produced in vitro by liver microsomes from rabbits (26,49,50) and rats (48) and consequently, higher amounts of NOH-4AAB (up to 3.9% (39) or 7% (52) of dose) or NOH-2AAF (up to 15% (51) or 30% (53)) were found in the urine of rats or rabbits, respectively. The high ferrihemoglobin-forming capabilities of the monocyclic hydroxamic acids NOH-4C1AA and NHP were discovered, when we determined their acute and chronic toxicities in the rat (54).…”
Section: N-arylacetohydroxamic Acids (N-hydroxy-n-arylacetamides)mentioning
confidence: 98%
“…Thus, because the relative proportion of the dose reacting with the target molecule also depends on the total body clearance of the compound (Gillette 1982), PCB pretreatment would probably not increase AAF-induced liver cancer. According to this, 3-methylcholanthrene is known to reduce the carcinogenic effect of AAF (Miller et al, 1958), probably because ring-hydroxylations are increased more than N-hydroxylations (Lotlikar et al, 1967 andJohnson et al, 1980).…”
Section: Holme Sp(derlund and Aunementioning
confidence: 99%