Repeated administration of carcinogen in critical developmental periods increases susceptibility of female Wistar : Han rats to mammary carcinogenesis induction

Analysis and knowledge of individual strain susceptibility of experimental animals to induction of carcinogenesis is important especially in regard to possibility of transfer of these facts to human pathology first of all to chemopreventive projects. Our group (A(HLERS) et al. [1]) reported very low sensitivity of female Wistar:Han rats to induction of mammary carcinogenes is by 7,12-dimethylbenz(a)anthracene (DMBA) and by N-methyl-N-nitrosourea ( NMU). The aim of this paper was to increase the sensitivity of females of t his strain to mammary carcinogenesis induction by repeated administration o f NMU in a dose 50 mg/kg of b.w. in critical periods: on 3-4 postnatal days , on 21 day (critical period for development of ductal parts of mammary gla nd) and between 50-55 days (maximal proliferation of whole gland). In compa rison with 38% incidence of mammary tumors after the single dose and 65% in cidence after 3 subsequent doses between 50 60 days, the combination of adm inistration (only) on 21 day and between 50-55 postanatal days resulted in 88% incidence - the sensitivity of animals reached the level of highly susc eptible rat strains. The latency period was significantly increased in grou ps with NMU given on 3-4, 21 days and between 45-55 days respectively, on 2 1 day and between 45-55 days in comparison with control group (one dose of NMU). The tumor frequency per group and per animal in all groups with repea ted NMU administration was significantly higher than that of control group. The volume of tumors was not influenced either by repeated carcinogen appl ication or by time of its administration. These results expand the possibil ities of analysis of carcinogen effects in individual periods of rat postna tal development.