A simple, noninvasive test is proposed to measure the activity of the hepatocellular monooxygenase system in vivo. Elimination rates of the stable isotope 15N are measured in urine after an oral dose of the 15N-labeled phenacetin homologue [15N]methacetin. Different forms of obtaining and expressing results are investigated in order to determine optimum methodology and differentiation for clinical application in pediatrics. The best discriminating power and reliability of results are seen with the measurement of 15N elimination half-life. For follow-up, a more easily measured parameter--eliminated dose over 9 h--is sufficient. In the latter case, only total nitrogen and 15N contents of a collective urine sample are measured.

Acetamides↗

PubMedDate not supplied

The role of metabolism of chemicals with respect to carcinogenicity tests.

Precarcinogens can be activated to carcinogenic effective compounds--ultimate carcinogens--by mammalian enzymes in vivo. In in vitro short-term tests, estimating effects which correlate with carcinogenicity in vivo of a chemical, these enzymes are represented by liver postmitochondrial fractions (S9) added to the test system. For the characterization and standardization of these S9 preparations we estimated certain enzymes involved in activating process: benzo(a)pyrene hydroxylase, the N-demethylases of dimethylnitrosamine, 4-dimethylaminoazobenzene and for a comparison, ethylmorphine as well as the azoreductase with 4-dimethylaminoazobenzene as a substrate. In order to get preparations with high enzyme activities, the animals such as rats, mice, hamsters and rabbits were pretreated by inducers such as polychlorinated biphenyls, phenobarbital, and 3-methylcholanthrene. We have observed species-specific differences in basic enzymatic patterns and in the degree of enzyme activities after induction. So it is principally possible to find out, whether or not a distinct animal species or strain is capable of metabolizing certain precarcinogens. Our aim is to optimize the evaluation of the carcinogenic risk of chemicals to humans by including human enzyme preparation in short-term tests.

2-Acetylaminofluorene↗

PubMedDate not supplied

Testing of chemicals for carcinogenic activities and some problems related to the assessment of carcinogenic risks to men.

It is recognized that many human cancers are influenced by environmental factors. Therefore, testing of chemicals for carcinogenic activities represents an important part of comprehensive toxicological examinations. Procedures to be employed in bioassays for carcinogenicity will be discussed. Short-term tests should be utilized as screening methods to select suspected chemicals which should or must be further tested in long-term animal experiments. Animal tests can predict carcinogenicity in man. Any substance which is shown conclusively to cause tumors in animals should be considered carcinogenic and therefore a potential hazard for man, but tests on experimental animals cannot provide irrefutable proof of the safety or carcinogenicity of a substance for the human species. Therefore, some of the problems related to the assessment of carcinogenic risks by chemicals will be discussed.

Animals↗