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Enhancing effect of various hepatocarcinogens on induction of preneoplastic glutathione S-transferase placental form positive foci in rats--an approach for a new medium-term bioassay system.

Abstract：

:A large series of assays of the hepatocarcinogenic potential of 112 different compounds were carried out using a rapid bioassay system developed in this laboratory based on the two-step concept of hepatocarcinogenesis. Rats were initially given a single dose (200 mg/kg) of diethylnitrosamine (DEN) i.p. and starting 2 weeks later were treated with test compounds for 6 weeks and then killed, all rats being subjected to two-thirds partial hepatectomy (PH) at week 3. Carcinogenic potential was scored by comparing the number and area per cm2 of induced glutathione S-transferase placental form-positive (GST-P+) foci in the liver with those of the corresponding control group given DEN alone. Positive was scored for a significant increase in the value of GST-P+ foci, negative for no change or a decrease. Results were compared to reported Salmonella/microsome and long-term carcinogenicity test findings. Of the liver carcinogens, 10 out of 11 (90.9%) mutagenic, and 11 out of 13 (84.6%) non-mutagenic compounds gave positive results (mean, 87.5%). Carcinogens other than the hepatocarcinogens gave less positive results (two out of 17, 11.8%). None of the compounds reported as non-carcinogenic demonstrated positivity suggesting that the assay system does not suffer from the disadvantage of false-positive results. The protocol system also provided information concerning the inhibitory potential of compounds such as anti-oxidants. It is concluded that the present experimental protocol which requires far fewer animals and shorter duration than a long-term carcinogenicity test has practical applications for the rapid and economical screening of environmental hepatocarcinogens and their inhibitory agents.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Ito N,Tsuda H,Tatematsu M,Inoue T,Tagawa Y,Aoki T,Uwagawa S,Kagawa M,Ogiso T,Masui T

doi

10.1093/carcin/9.3.387

subject

Has Abstract,Author List Incomplete

pub_date

1988-03-01 00:00:00

pages

387-94

issue

eissn

0143-3334

issn

1460-2180

journal_volume

pub_type

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Enhancing effect of various hepatocarcinogens on induction of preneoplastic glutathione S-transferase placental form positive foci in rats--an approach for a new medium-term bioassay system.