W. Yu et al., Preconception urethane or chromium(III) treatment of male mice: Multiple neoplastic and non-neoplastic changes in offspring, TOX APPL PH, 158(2), 1999, pp. 161-176
Increase in neoplasia in offspring after preconception exposure of parents
presents puzzling features such as high frequency of effects and lack of Me
ndelian inheritance. The present study examined the hypothesis that preconc
eption carcinogenesis involves an increase in the rate of occurrence of neo
plasms with a spontaneous incidence. Male NIH Swiss mice (12 per group) wer
e exposed 2 weeks before mating (once, ip) to urethane (1.5 g/kg) or chromi
um(III) chloride (1 mmol/kg). Offspring (48-78/sex/group) were examined for
all grossly apparent changes when moribund or at natural death, followed b
y histopathological diagnosis and statistical analysis. Significant exposur
e-related changes occurred in multiple organs. Ten to 20 percent of offspri
ng showed changes related to paternal exposure, including at least one sire
d by most treated males. Pheochromocytomas occurred in both male: and femal
e offspring after both treatments, with none in controls. These neoplasms a
re rare in mice and suggest endocrine dysfunction as a component of preconc
eption carcinogenesis. This was supported by increases in thyroid follicula
r cell and Harderian gland tumors, ovarian cysts, and uterine abnormalities
. Lung tumors were increased in female offspring only. Effects seen in offs
pring only after paternal urethane exposure were an increase in preneoplasi
a/neoplasia in the glandular stomach (males) and in females, increased lymp
homa but decreased incidence of histiocytic sarcoma. Increases in incidence
of male reproductive gland tumors and of renal non-neoplastic lesions occu
rred only after chromium exposure. Thus, preconception exposure of fathers
to toxicants had a significant impact on both neoplastic and nonneoplastic
changes in almost all tissues in which these lesions often occur naturally
during the aging process. (C) 1999 Academic Press.