1,2,3-Trichloropropane (TCP) is a multispecies, multisite carcinogen w
hich has been found to be an environmental contaminant. In this study,
we have characterized and measured DNA adducts formed in vivo followi
ng exposure to TCP. [C-14]TCP was administered to male B6C3F1 mice and
Fischer-344 rats by gavage at doses used in the NTP carcinogenesis bi
oassay. Both target and nontarget organs were examined for the formati
on of DNA adducts. Adducts were hydrolyzed from DNA by neutral thermal
or mild acid hydrolysis, isolated by HPLC, and detected and quantitat
ed by measurement of radioactivity. The HPLC elution profile of radioa
ctivity suggested that one major DNA adduct was formed. To characteriz
e this adduct, larger yields were induced in rats by intraperitoneal a
dministration of TCP (300 mg/kg). The DNA adduct was isolated by HPLC
based on coelution with the radiolabeled adduct, and compared to previ
ously identified adducts. The isolated adduct coeluted with S- (hydrox
ymethyl)-2-(N-7-guanyl)-ethyl]-glutathione, an adduct derived from the
structurally related carcinogen 1,2-dibromo-3-chloropropane (DBCP). A
nalysis by electrospray mass spectrometry suggested that the TCP-induc
ed adduct and the DBCP-derived adduct were identical. The C-14-labeled
DNA adduct was distributed widely among the organs examined. Adduct l
evels varied depending on species, organ, and dose. In rat organs, add
uct concentrations for the low dose ranged from 0.8 to 6.6 mu mol per
mol guanine and from 7.1 to 47.6 mu mol per mol guanine for the high d
ose. In the mouse, adduct yields ranged from 0.32 to 28.1 mu mol per m
ol guanine for the low dose and from 12.2 to 208.1 mu mol per mol guan
ine for the high dose. The relationship between DNA adduct formation a
nd organ-specific tumorigenesis was unclear, Although relatively high
concentrations of DNA adducts were detected in target organs, several
nontarget sites also contained high adduct levels. Our data suggest th
at factors in addition to adduct formation may be important in TCP-ind
uced carcinogenesis.