ANALYSES OF METABOLIC ACTIVATION/INACTIVATION OF SELECT CHEMICAL CARCINOGENS

Project: Research project

Project Details

Description

The studies to be carried out under this limited-scope application are a
continuation of our previous and current studies on the electrophilic
(active) and non-electrophilic (inactive) metabolites of three selected
groups of chemical carcinogens and their DNA adducts.

1. The first group consists of ethyl carbamate, vinyl carbamate, vinyl
carbamate epoxide, and the related human liver carcinogen, vinyl
chloride and its epoxide. Considerable medical exposure of
Japanese patients to ethyl carbamate occurred unwittingly in Japan
from 1950 to 1975. Humans are also exposed to very low to low
dietary levels of ethyl carbamate present in many foods and
beverages derived from ethanolic fermentations. We wish to study
the metabolism and DNA adducts of these hepatic carcinogens in
rodent and human tissues.

2. The second group consists of the asarones and the precocenes that
occur naturally in certain spice herbs and in certain plants as
insecticides, respectively. Our previous work has included
detailed studies of specific allylbenzenes (safrole, estragole, and
methyl eugenol) that occur in many spice herbs. These compounds
are activated via hydroxylation of the benzylic carbon followed by
esterification to form electrophilic sulfuric acid esters. The
asarones and the precocenes are propenylbenzenes. Our initial work
suggests that the hydroxylation-ester pathway apparently does not
apply to these compounds. We particularly wish to study the
probable electrophilic epoxide metabolites and DNA adducts of these
compounds.

3. The third group consists of the carcinogens S-vinyl-homocysteine
(vinthionine) and S-ethyl-homocysteine (ethionine). They appear to
have interesting differences in activation in carcinogenesis and in
mutagenic properties. Our previous work included the first
synthesis and discovery of the carcinogenicity and mutagenicity of
vinthionine.
StatusNot started