Differential sensitivities of spermatogonial and postspermatogonial cell stages of the mouse to induction of unscheduled DNA synthesis by ethyl- and methyl-nitrosourea.

An autoradiographic procedure was used to measure unscheduled DNA synthesis (UDS, DNA repair synthesis) in spermatogonial and postspermatogonial cell stages of mice after treatment with two doses of N-ethyl-N-nitrosourea (ENU) and N-methyl-N-nitrosourea (MNU). Significant levels of UDS were measured in type A spermatogonia, meiotic spermatocytes, round spermatids, and early elongating spermatids but not in mature spermatids. The extent of UDS varied according to the germ cell stage and the dose.

Induction of specific-locus and dominant lethal mutations in male mice by ifosfamide (Holoxan).

Ifosfamide induced dominant lethal mutations in spermatozoa of mice at doses of 200 and 300 mg/kg and in spermatids and spermatocytes at 600 mg/kg. The highest dose also induced specific-locus mutations in post-spermatogonial germ-cell stages of mice but not in spermatogonial stem cells. The nature of the induced mutations suggests they are intergenic.

Induction of specific-locus and dominant lethal mutations in male mice by 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU).

1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) induced dominant lethal and specific-locus mutations in male mice. For both compounds the germ cell stage sensitive to the induction of dominant lethal mutations was dose dependent. A dose of 5 mg BCNU per kg b.

The effect of the interval between dose applications on the observed specific-locus mutation rate in the mouse following fractionated treatments of spermatogonia with ethylnitrosourea.

Our earlier analyses have suggested an apparent threshold dose-response for ethylnitrosourea-induced specific-locus mutations in treated spermatogonia of the mouse to be due to a saturable repair process. In the current study a series of fractionated-treatment experiments was carried out in which male (102 x C3H)F1 mice were exposed to 4 x 10, 2 x 40. 4 x 20 or 4 x 40 mg ethylnitrosourea per kg body weight with 24 h between applications; 4 x 40 mg ethylnitrosourea per kg body weight with 72 h between dose applications; and 2 x 40, 4 x 20 and 4 x 40 mg ethylnitrosourea per kg body weight with 168 h between dose applications.

Synthesis report of the step project detection of germ cell mutagens.

The project 'Detection of Germ Cell Mutagens' was designed with three major goals: (1) Detection and characterization of germ-cell mutagens; (2) standardization and validation of new germ-cell tests; and (3) development of a data base on germ-cell mutagenicity. All three goals were achieved. The classical germ-cell tests were applied to characterize the genetic effects of acrylamide (AA), 1,3-butadiene (BD), trophosphamide (TP) and urethane (UR).