Micronuclei and other nuclear anomalies induced in various organs by diethylnitrosamine and 7,12-dimethylbenz[ a]anthracene

Abstract

(Accepted 11 February 1986) A large number of carcinogens have been assayed for genotoxic activity in the rodent bone marrow micronucleus test (Heddle et al., 1983). However, the test appears to lack sensitivity towards a number of carcinogens. One reason for this insensitivity may be that the bone marrow is not a target organ for these carcinogens and thus there is a distinct need to monitor genotoxic effects in additional organs or tissues of the treated animal (Ashby, 1983). Genotoxic agents are capable of causing a variety of cell nucleus changes such as pyknosis, karyorrhexis, aptosis as well as micronuclei (Matter and Schmid, 1970; Wargovich et al., 1983) and recently it has been shown that some carcinogens, which have little or no effect on the bone marrow, are capable of causing micronuclei and nuclear anomalies in the cells of other organs (Tates et al., 1980; Goldberg et al., 1983; Ronen et al., 1983). In this study we have examined the ability of diethylnitrosamine (DEN) and 7,12-dimethyl- benz[a]anthracene (DMBA) to induce nuclear anomalies in the urinary bladder, colon, liver and lung of weanling mice and have compared this with micronucleus formation in polychromatic erythrocytes of the bone marrow of the same animals 24 h after administration. It was found that DMBA induced nuclear anomalies in the bone marrow and colon while DEN induced anomalies in the bladder, colon, liver and lung but not the bone marrow. Materials and methods Weanling (21 days old, weighing 12 g) Swiss Crl: CD ® -1 (ICR) BR outbred albino mice were ob- tained from Charles River UK Ltd. Weanling mice were chosen because they have been reported to be more susceptible to tumour induction by a variety of chemicals (Vesselinovitch et al., 1979), and also the expected higher numbers of dividing cells in the somatic tissues would possibly enhance their sen- sitivity to genotoxins. The animals were allowed tap water and standard laboratory diet throughout the experiment. DEN (CAS registry 55-18-5, pfs grade) and DMBA (CAS registry 53-97-6, approx. 950-/0 pure) were obtained from Sigma. DEN was dissolved and DMBA was suspended in the vehicle, aqueous 1 °70 methylcellulose just prior to administration by oral gavage in a dosage volume of 20 ml per kg bodyweight. The dose levels used were chosen on the basis of a small preliminary acute toxicity test and were approximately the maximum tolerated dose (MTD/24 h). The animals were dosed when 21 days old and sacrificed 24 h later. 5 male and 5 female mice were selected at random from the surviving animals in each group (some mortalities occurred in the DEN- treated group). 5 male and 5 female mice treated with the vehicle alone formed a control group. Bone marrow smears were made from the selected animals and stained with Giemsa. All 0165-7992/86/$ 03.50 © 1986 Elsevier Science Publishers B.V. (Biomedical Division)