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Titolo:
MUTATIONAL RESPONSE AT THE SPLENIC T-LYMPHOCYTE HPRT LOCUS IN MICE TREATED AS NEONATES - CONTRASTING EFFECTS OF THE CARCINOGENS N-ETHYL-N-NITROSOUREA, DIMETHYLNITROSAMINE, AND 2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE
Autore:
DASS SB; HEFLICH RH; CASCIANO DA;
Indirizzi:
NATL CTR TOXICOL RES,DIV GENET & REPROD TOXICOL JEFFERSON AR 72079
Titolo Testata:
Environmental and molecular mutagenesis
fascicolo: 3, volume: 31, anno: 1998,
pagine: 243 - 247
SICI:
0893-6692(1998)31:3<243:MRATST>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
TRANSGENIC MICE; IN-VIVO; FISCHER-344 RATS; INVIVO EXPOSURE; FOOD MUTAGENS; MOUSE MODEL; BONE-MARROW; INDUCTION; FREQUENCY; ETHYLNITROSOUREA;
Keywords:
NEONATAL MICE; HPRT; T-LYMPHOCYTE MUTATION; N-ETHYL-N-NITROSOUREA; DIMETHYLNITROSAMINE; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
35
Recensione:
Indirizzi per estratti:
Citazione:
S.B. Dass et al., "MUTATIONAL RESPONSE AT THE SPLENIC T-LYMPHOCYTE HPRT LOCUS IN MICE TREATED AS NEONATES - CONTRASTING EFFECTS OF THE CARCINOGENS N-ETHYL-N-NITROSOUREA, DIMETHYLNITROSAMINE, AND 2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE", Environmental and molecular mutagenesis, 31(3), 1998, pp. 243-247

Abstract

The newborn mouse tumorigenicity assay, which involves the treatment of animals during the first two weeks after birth and monitoring tumorinduction after a year, has been suggested as a cost- and time-effective alternative to the conventional two year rodent bioassay. In orderto evaluate whether or not lymphocyte hprt mutant induction is an accurate predictor of carcinogenicity in the assay, we determined the frequencies of 6-thioguanine-resistant (TG(r)) lymphocytes in the spleensof mice neonatally treated with the carcinogenic mutagens N-ethyl-N-nitrosourea (ENU), dimethylnitrosamine (DMN), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhlP). Male C57BL/6 pups were injected on postnatal days 8 and 15, and the frequency of TG(r) T-lymphocytes was measured in groups of three animals, sacrificed periodically up to 31 weeks post-treatment. Compared to background frequencies of 1.1-2.9 x 10(-6), mutant frequencies (MFS) reached 155.1 x 10(-6) following a cumulative dose of 49 mg ENU/kg body weight and 172.3 x 10(-6) followinga cumulative dose of 142 mg ENU/kg. These results show that TG(r) lymphocyte mutations can be induced and measured in mice treated as neonates and that the induced MFs found for mice treated neonatally with ENU are comparable with frequencies reported For the treatment of adult animals with the some chemical. In contrast, treatment with the promutagenic and procarcinogenic compounds DMN (at a maximum concentration of 10.5 mg/kg) and PhlP (26.2 mg/kg) did not result in on increase in lymphocyte MF, suggesting that reactive metabolites of these compounds may not be reaching cells that are sensitive for mutation fixation. The results indicate that the lymphocyte hprt assay may fail to predict the carcinogenicity of some test chemicals in the neonatal mouse bioassay. (C) 1998 Wiley-Liss, Inc.

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Documento generato il 09/04/20 alle ore 05:35:18