Induction Of Heritable Translocations Research Articles

Quantitative estimation of the genetic risk associated with the induction of heritable translocations at low‐dose exposure: Ethylene oxide as an example

This paper explores how quantitative risk assessment methods might be extended to analysis of risks to the human germ line. High inhalation exposures to ethylene oxide are reported to cause heritable translocations in male mice with a steep and nonlinear dose-response-curve. We explore quantitative estimation of risk to humans from low exposures based on these animal data, addressing questions of tissue dosimetry for this alkylating agent, expected equivalency of doses across species, germ-cell sensitivity, and extrapolation of dose-response relationship to low exposure levels. Various dose-response models are discussed in terms of their applicability to genetic end points and their ability to reflect the underlying basis of induced heritable translocations.

Acrylamide: Induction of heritable translocations in male mice

Acrylamide (AA), known to induce dominant lethals in male rodents, was studied in the mouse heritable translocation test by using intraperitoneal injections on 5 consecutive days. Matings on days 7-10 following the last injection yielded a high frequency of translocation carriers in the F1 male population, which demonstrated that acrylamide is an effective inducer of translocations in postmeiotic germ cells. As an inducer of both dominant lethals and heritable translocations in late spermatids and early spermatozoa, AA is similar to alkylating agents such as ethylmethanesulfonate and ethylene oxide. However, AA's chemical structure, the nature of adducts formed with DNA, and it lack of mutagenicity in bacteria suggest a different mechanism as the basis for AA's germ cell mutagenicity.

Studies on chemical induction of chromosomal aberrations in postcopulation germ cells and zygotes of female mice. II. Induction of heritable translocations.

The induction of heritable translocations with chemicals in postcopulation germ cells of female mice was investigated. In the methyl methanesulfonate (MMS)-treated group (100mg/kg), 14 partially sterile and 5 sterile males out of 118 F1 male progeny were found. In contrast, in the mitomycin C (MC)- treated group (3mg/kg and 4mg/kg) the frequencies were low. These results indicate that the yield of heritable translocations parallels the formation of chromosome-type aberrations at the first cleavage reported previously.

Genetic effects of benzene in Drosophila melanogaster males.

Benzene is one of the few chemicals which induces chromosomal aberrations but does not induce point mutations. The most sensitive end point in Drosophila, sex-linked recessive lethal mutations, however, has not yet been studied. Information on induction of heritable translocations and crossing-over is also not yet available for this compound in Drosophila. Experiments were therefore undertaken to investigate benzene induced sex-linked recessive lethal mutations, heritable translocations, and crossing-over in Drosophila males.

Lack of association between induction of dominant-lethal mutations and induction of heritable translocations with benzo[ a]pyrene in postmeiotic germ cells of male mice

Benzo[ a]pyrene was tested for induction of dominant-lethal mutations in germ cells of male mice. Clear-cut dominant-lethal effects were induced in middle and early spermatoza. In contrast to the dominant-lethal effects observed the study showed no detectable increase in hertiable translocations for these stages over the spontaneous level. Thus, the results provide another example of a chemical mutagen that is effective in inducing dominant-lethal mutations but relatively ineffective in inducing heritable translocations in male postmeiotic germ cells.

Induction of heritable translocations with methyl methanesulfonate in male mice

Induction of heritable translocations with methyl methanesulfonate in male mice

Induction of heritable translocations with methyl methanesulfonate in male mice

Induction of heritable translocations with methyl methanesulfonate in male mice