@entity3101 (GF) has been in use for more than 30 years as a pharmaceutical drug in @entity1 for the treatment of @entity9202 . Animal studies give clear evidence that it causes a variety of acute and chronic toxic effects, including liver and @entity259 in rodents, abnormal germ cell maturation, teratogenicity, and embroyotoxicity in various species. No sufficient data from @entity1 studies are available at present to exclude a risk in @entity1 : therefore, attempts were made to elucidate the mechanisms responsible for the toxic effects of GF and to address the question whether such effects might occur in @entity1 undergoing GF therapy. It is well documented that GF acts as a spindle poison and its reproductive @entity137 as well as the induction of numerical chromosome aberrations and of micronuclei in somatic cells possibly may result from disturbance of microtubuli formation. Likewise, a causal relationship between @entity2007 and @entity5 has been repeatedly postulated. However, a critical survey of the data available on aneuploidogenic chemicals revealed insufficient evidence for such an association. Conceivably, other mechanisms may be responsible for the carcinogenic effects of the drug. The induction of @entity259 in @entity35 by GF is apparently a consequence of the decrease of thyroxin levels and it is unlikely that such effects occur in GF-exposed @entity1 . The appearance of @entity157 ( @entity157 ) in @entity19 on GF-supplemented diet is preceded by various biochemical and morphological changes in the liver. Among these, @entity99 is prominent, it may result from inhibition of @entity7886 and (compensatory) induction of ALA synthetase. GF-induced accumulation of @entity7889 in @entity19 liver is followed by cell damage and @entity39 and inflammatory processes. Similar changes are known from certain @entity1 porphyrias which are also associated with an increased risk for @entity157 . However, the porphyrogenic effect of GF therapy in @entity1 is moderate compared with that in the @entity19 model, although more detailed studies should be performed in order to clarify this relationship on a quantitative basis. A further important effect of GF-feeding in @entity19 is the formation of Mallory bodies (MBs) in hepatocytes. These cytoskeletal abnormalities occur also in @entity1 , although under different conditions; their appearance is associated with the induction of @entity409 and @entity157 . Chronic @entity409 associated with @entity6050 and @entity23768 formation, enhanced cell proliferation, @entity382 , and enzyme induction all may contribute to the hepatocarcinogenic effect of GF in @entity19 . In conclusion, further investigation is required for adequate assessment of health risks to @entity1 under GF therapy.

Toxic effects of XXXX : disease models, mechanisms, and risk assessment.

@entity1 :: ('9606', 'Species') :: ['humans', 'human'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity'] @entity2007 :: ('MESH:D000782', 'Disease') :: ['aneuploidy'] @entity9202 :: ('MESH:D003881', 'Disease') :: ['dermatomycoses'] @entity3101 :: ('MESH:D006118', 'Chemical') :: ['Griseofulvin'] @entity99 :: ('MESH:D056486', 'Disease') :: ['hepatic porphyria'] @entity5 :: ('MESH:D009369', 'Disease') :: ['cancer'] @entity19 :: ('10090', 'Species') :: ['mice', 'mouse'] @entity39 :: ('MESH:D009336', 'Disease') :: ['necrotic'] @entity7889 :: ('MESH:D011166', 'Chemical') :: ['porphyrins'] @entity409 :: ('MESH:D008107', 'Disease') :: ['liver disease', 'liver damage'] @entity382 :: ('MESH:D006529', 'Disease') :: ['liver enlargement'] @entity35 :: ('10116', 'Species') :: ['rats'] @entity157 :: ('MESH:D006528', 'Disease') :: ['HCC', 'hepatocellular carcinomas'] @entity259 :: ('MESH:D013964', 'Disease') :: ['thyroid tumors', 'thyroid cancer'] @entity23768 :: ('OMIM:613729', 'Disease') :: ['MB'] @entity7886 :: ('2235', 'Gene') :: ['ferrochelatase'] @entity6050 :: ('MESH:D011164', 'Disease') :: ['porphyria']
@entity3101 :: (MESH:D006118,Chemical) :: ['griseofulvin']
