Lack of clastogenic activity of aniline hydrochloride in the mouse bone marrow

Abstract

Aniline has been reported to be positive in the mouse bone marrow micronucleus test. This finding is inconsistent with its lack of carcinogenicity in this species. Micronuclei can arise by mechanisms that do not involve direct interaction with DNA, e.g. induction of aneuploidy or stimulation of erythropoiesis. However, clastogenic materials would be expected to demonstrate an increased level of chromosomal damage in dividing precursor erythroblasts. In the present study we have investigated the ability of aniline HCl to induce chromosome aberrations in bone marrow metaphase cells. No evidence of clastogenicity was observed in this study. This suggests that the activity seen in earlier micronucleus assays may have arisen by a mechanism not involving direct DNA interaction. Aniline is known to be toxic towards the erythropoietic system and the possibility exists that micronuclei may be produced as a result of this toxicity.

High-dose clastogenic activity of aniline in the rat bone marrow and its relationship to the carcinogenicity in the spleen of rats

“…In a very recent study employing the most rigid dosing regimen (two intraperitoneal injections at dose levels up to 380 mg/kg), no increase in the incidence of chromosomal aberrations could be found in mice (Jones and Fox 2003), thus suggesting that aniline is nonclastogenic in mice.…”

Assessment of the in vivo genotoxicity of isomers of dinitrotoluene using the alkaline Comet and peripheral blood micronucleus assays

“…Although it did not pose a problem in tests conducted with 2,4,6-trinitrotoluene (TNT) which gave clearly negative results, methemoglobinemia has been cited as a contributor to false positive results in micronucleus assays [31][32][33]. Two types of methemoglobinemia-associated false positive results occur in flow cytometry assays: an artificial increase in MN-RET counts measured by flow cytometry due to autofluorescence; and an actual, though non-genotoxic, increase in MN-RET that is due to disturbance of erythropoiesis.…”

“…The increase in production of RETs possibly resulting from tissue hypoxia induced stimulation of erythropoietin secretion [33]. Accelerated proliferation and differentiation of erythrocytes can lead to increased MN-RETs due to more opportunities for spontaneous errors in cell division and errors during enucleation [32,33]. Stimulation of erythropoiesis by erythropoietin may also reduce the efficiency of DNA repair and, through the suppression of apoptosis, possibly enable the survival of damaged cells [34,35].…”

“…Stimulation of erythropoiesis by erythropoietin may also reduce the efficiency of DNA repair and, through the suppression of apoptosis, possibly enable the survival of damaged cells [34,35]. Treatment with erythropoietin and stimulation of erythropoiesis has been shown in mice to increase micronuclei frequency, theoretically as a result of reduced efficiency of DNA repair [32]. In the case of aniline, however, the compound did not exhibit in vivo clastogenic activity in the mouse bone marrow, suggesting a non-genotoxic origin for the observed micronuclei [32].…”

“…Treatment with erythropoietin and stimulation of erythropoiesis has been shown in mice to increase micronuclei frequency, theoretically as a result of reduced efficiency of DNA repair [32]. In the case of aniline, however, the compound did not exhibit in vivo clastogenic activity in the mouse bone marrow, suggesting a non-genotoxic origin for the observed micronuclei [32]. In the present study, several isomers (2,6-DNT, 2,4-DNT, 2,5-DNT) demonstrate increases in reticulocytes, while only 2,5-DNT has apparent, though likely false, increases in micronuclei.…”