Very low sensitivity of Wistar:Han female rats to chemocarcinogens in mammary carcinogenesis induction

Recently a great variability of various mouse and rat strains in the sensitivity for mammary tumors induction by means of physical (ionizing radiation) or chemical (mostly 7,12-dimethylbenz/a/anthracene, DMBA and N-methyl-N-nitrosourea, NMU) initiating agents was noted. The categorization into four groups was recommended in rats; the first group with high sensitivity (the incidence of tumors practically 100%, the frequency of tumors per entire treated group 2.0), the second with average type of sensitivity (incidence below 100%, frequency between 1.0-2.0), the third with low sensitivity (frequency 0.3-.4) and the fourth with zero sensitivity as the response to single standard dose of DMBA. After initial observations we decided to analyze the sensitivity to mammary carcinogenesis in the female rats of Wistar:Han strain, used frequently in central European region. Twenty mg of DMBA by gavage as single dose, or three-times 10 mg by gavage as repeated consecutive doses in three-day intervals, or 30 mg/kg b.w. of NMU intraperitoneally were administered, always between 50-55 postnatal days (single doses) or between 50-60 days (repeated doses of DMBA). The average incidence of mammary tumors did not exceed 10% and the entire group tumor frequency was about 0.1 for both carcinogens used. The data allowed us to indicate the female Wistar:Han rats as animals with "very low" sensitivity for the initiation of mammary tumors by single dose of DMBA or NMU; being in this way very close to the insensitive strains. The fact of "sensitivity" improvement to higher range after repeated doses of DMBA indicated a non-genetic background of the changed sensitivity. Our results support the need to use more then one rat strain for initiation of mammary carcinogenesis, and for assessing the bright range of the biological response. In this situation the concept of "multi-strain" assay seems to be the optimal.