GENETICS OF NEOPLASIA 251 



We have observed carcinoma of the uterus in C3H x C57BL hybrids and Allen and 

 Gardner 9 have reported a rather high occurrence of the neoplasm in CBA x C57BL 

 hybrids treated with estrogen. This suggests the value of hybridizing our present 

 strains to obtain a population from which a strain bearing the desired neoplasm might 

 be selected. It also suggests the use of a carcinogen, in this case estrogen, in bringing 

 to expression underlying genetic factors for selection. 



Gastrointestinal cancer is the most prevalent cancer of man, but we have no 

 strain of laboratory animal in which it can be studied adequately. Since carcinoma of 

 the glandular stomach of the rat has been produced by injection of the carcinogenic 

 hydrocarbons and carcinoma of the small intestine has been induced in mice by 

 feeding these carcinogens, in this case also a program of selection with the use of the 

 carcinogen to bring out the expression of the genes might result in a strain in which 

 the neoplasm eventually appeared spontaneously. Strong's strain BRS in which the 

 gastric lesion arose following methylcholanthrene was later found to develop the lesion 

 spontaneously. 



The pulmonary tumor of the mouse, while a very valuable tumor for basic genetic 

 studies of neoplasia, is not comparable with the bronchiogenic carcinoma of man to 

 which so much attention is directed today. Bronchiogenic carcinomas can be in- 

 duced, however, in a mash of murine pulmonary tissue implanted subcutaneously 

 along with crystals of carcinogen, 1224 and it is possible that this technique might be of 

 value in selecting genes for this type of neoplasm and fixing them in a strain. 



SPECIAL SUBLINES 



Sublines free from agents normally passed through the placenta or milk can be of 

 considerable value in separating genetic from nongenetic effects as illustrated by the 

 lines free of the mammary tumor agent, or virus, that is normally transferred through 

 the milk. Those passed through the milk can be satisfactorily eliminated by foster 

 nursing on a strain lacking the agent when one does not want to go to complex germ- 

 free procedures. It is advisable to take the young by cesarean section to insure against 

 their nursing at all upon their own mothers. For survival the fetuses should be 

 removed within 24 hours of term or preferably less. This time can be estimated by 

 observing the vaginal plug when one has some knowledge of the exact gestation period 

 for the strain. However, one experienced in the care of mice can judge the time 

 almost as well by direct observation of the pregnant female without having observed 

 the vaginal plug. 



Our own subline of C3Hf mice was started by foster nursing a litter of C3H mice 

 after cesarean birth from their high-mammary-tumor C3H mother with the agent, on a 

 C57BL female without the agent. The subline is now in the forty-fifth inbred genera- 

 tion since the original foster-nursed litter, but mammary tumors have continued to 

 appear at a relatively low incidence ranging in breeding females from 14 per cent in 



