A laboratory demonstration of transmission and prevention of hereditary tumors in hybrid rats

A42

Hereditary tumors develop spontaneously through endogenous mechanisms that are not preventable and rarely curable. Herditary tumors were originally identified by familial clustering (multiple cases per family), by onset at early age, by aggressive growth patterns, and by speculations that they were transmitted in dominant mode from fathers to sons by inheritance. However benign tumors also express hereditary characteristics. Two disparate strains of inbred rats were selected, each developing spontaneously up to age 24 months, differences in tumor type, in organ site, and in optimal level of endogenous testosterone for tumor development. Male Fischer (F344) rats that develop benign interstitial testicular (Leydig cell) tumors (ITT) linked to low physiological levels of endogenous testosterone (T) and prevented by high levels of T, were mated with female Lobund-Wistar (LW) rats, a strain that develops prostate cancer (PC) linked to abnormally high levels of endogenous T and prevented by early T-deprivation. Low physiological levels of T are ~ 250 pg/ml serum and abnormal high levels of T are >1800 pg/ml serum. At age 24 months, the male hybrids carried low levels of T, and 50% of the F1 hybrids developed overt ITT, a pattern that was repeated in F2 and F3 hybrids. Hybrids were free of overt and of microscopic biomarkers of PC, however a) a subset of hybrids (37%) developed overt PC following IV inoculation of mutagenic methylnitrosourea plus implants of exogenous testosterone propionate ,and b) like LW control rats, hybrids were susceptible to the unique hormone refractory PC (PAIII) transplanted cell, that was rejected by control Fischer rats. This innovative experiment a) confirms the speculations of male to male transmission of ITT in hybrids linked to low levels of T and b) revealed the inherited genomic potential in hybrids derived from both of their parents.