Quantitative predictivity of carcinogenicity of the autoradiographic repair test (primary hepatocyte cultures) for a group of 80 chemicals belonging to different chemical classes.

نویسندگان

  • C Bolognesi
  • M Taningher
  • S Parodi
  • L Santi
چکیده

In this work we have investigated the correlation existing between a short-term genotoxicity test (DNA repair in rat liver cells) and carcinogenicity in rodents. The work is in the framework of a line of thinking that considers as a possibility the utilization of the quantitative component of the information obtained from genotoxicity tests. In a preliminary report for 25 compounds belonging to different chemical classes, a correlation coefficient of 0.36 was found between carcinogenic potency in small rodents and potency in autoradiographic repair. This level of correlation is comparable with similar levels found for many other short-term tests: Ames test, alkaline DNA fragmentation in vivo, DNA adducts in vivo, morphological transformation in vitro and SCE induction in vivo. Obviously, since only 25 compounds were examined, assessment was rather uncertain, and the subdivision of the set into subsets for different chemical classes would have generated groups too small for a meaningful statistical analysis. With a much larger set (80 compounds) we hoped to be able to discriminate different predictivities for different chemical classes. This seems important because the test could be much more suitable for one given class than for another. Previous investigations with different short-term tests have shown that these differences can indeed exist and be very great. In this respect it is potentially very encouraging that the test considered here showed a fair correlation with carcinogenic potency for aromatic amines. Many other tests that we have examined so far have shown little or no predictivity for this important class of chemicals.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Structure-activity relations: maximizing the usefulness of mutagenicity and carcinogenicity databases.

The most important criteria for the development and analysis of databases for elucidating the structural bases of toxicological activity include the integrity of the databases with respect to uniformity of the experimental protocol and interpretation of the test results and inclusion of chemicals representing different chemical classes and differing mechanisms of action. Within these criteria, ...

متن کامل

Chemical quantification of unscheduled DNA synthesis in cultured hepatocytes as an assay for the rapid screening of potential chemical carcinogens.

Technical modifications of the quantitative determination of unscheduled DNA synthesis in cultured hepatocytes are described which allow for the rapid identification of potentially carcinogenic chemicals on a large-scale screening basis. The test is based on the biochemical quantification of [methyl-3H]thymidine incorporation into DNA in the presence of hydroxyurea following isolation of nuclei...

متن کامل

Detection of chemical carcinogens by unscheduled DNA synthesis in rat liver primary cell cultures.

Unscheduled DNA synthesis was observed in primary rat liver cell cultures treated with members of five different classes of chemical procarcinogens requiring enzymatic activation as well as with a direct-acting carcinogen. In total, ten carcinogens and one related analog not commonly accepted as carcinogenic were active, while one weak carcinogen and four noncarcinogens were inactive. The produ...

متن کامل

Quantitative predictability of carcinogenicity of the covalent binding index of chemicals to DNA: comparison of the in vivo and in vitro assays.

The capability of covalent binding to DNA to predict the initiating potential of chemical carcinogens was compared for the assays performed in vivo (rodent liver DNA) and in vitro (purified DNA incubated in the presence of mouse and rat liver microsomes). A quantitative correlation between DNA adducts and carcinogenic potency was investigated. The in vivo assay appeared slightly, but not signif...

متن کامل

Use of primary cultures of adult rat hepatocytes on collagen gel-nylon mesh to evaluate carcinogen-induced unscheduled DNA synthesis.

The procarcinogen, 2-acetylaminofluorene, the direct-acting carcinogen, methyl methanesulfonate, and two other hepatocarcinogens, thioacetamide and urethan, were tested for their ability to elicit unscheduled DNA synthesis in adult rat hepatocytes maintained in primary culture on collagen gel-nylon mesh. The carcinogens, dissolved in dimethyl sulfoxide were added to 6-hr or to 28-hr cultures al...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • Environmental Health Perspectives

دوره 70  شماره 

صفحات  -

تاریخ انتشار 1986