화학물질의 생체내 단기발암성 검색에 관한 연구 1. 랫트에서 dietylnitrosamine과 2, 4-diaminotoluene에 의한 BrdU labeling index등 독성학적 변화

Possible Parameters for the Evaluation of Chemically Induced Carcinogenicity in In Vivo Short-term Screening Test 1. Physiological and Pathological Changes Including BrdU Labeling Index Following the Administration of Diethylnitrosamine and 2, 4-Diaminotoluene in Rats

To examine possible parameters for the evaluation of chemically induced carcinogenicity in vivo short-term screening test, diethylnitrosamine (DEN) and 2,4-diaminotoluene (2,4-DAT), both of these are known genotoxic hepatocarcinogens, were given to male SD rats at the doses of 12.5, 25.0 and 50.0mg/kg BW/day for 9 days with bromodeoxyuridine (12.5mg/kg BW/day) and thereafter, changes in body weight, organ weight and volume, hematologial and blood biochemical values, gross and histological findings and hepatocyte bromodeoxyuridine (BrdU) labeling index (LI) as a reliable marker for hepatocellular proliferation were measured. DEN produced extensive decrease in body weight gain, whereas no evidence of body weight gain was detected following the administration of 2,4-DAT. By the both of DEN and 2,4-DAT, relative liver weight (liver weight /body weight) significantly increased but relative liver volume (liver volum /liver weight) was not considerably changed. In the changes of hematological values, hemoglobin contents and hematocrits were elevated and mean corpuscular hemoglobin concentrations were reduced after the both treatment of DEN and 2,4-DAT, however, the other hematological values were not consistent between the two chemicals. Following the both administration of DEN and 2,4-DAT, blood biochemical values such as albumin and total portein contents were diminished and some blood enzyme activities such as alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyltranspeptidase (GGT) were increased. Also, paleness and friability of liver were observed as gross pathological findings and histopathological lesions such as necrosis and nuclear pleomorphism of hepatocyte, inflammatory cell infiltration into hepatic sinusoids and bile duct hyperplasia were shown. DEN produced obvious dose -dependent increase in BrdU LI, whereas increase by 2,4-DAT was not dose-dependent. In conclusion, among the present results, relative organ weight, blood biochemical values such as albumin, total protein, ALP, ALT, AST and GGT, histopathological findings and especially, BrdU LI may be used as useful parameters to evaluate the chemical carcinogenicity in in vivo short-term screening test.