Abstract: A rat with a disrupted Apc (adenomatous polyposis coli) gene is provided. The mutation can include an A to T transversion changing a lysine to a stop codon at codon 1137. Methods of generating the knockout rat are provided. Also provided is the offspring or progeny of that rat. In addition, methods of using these rats are provided, including methods for screening a carcinogen or a promoter of carcinogenesis, and methods for screening preventive and inhibitory agents of carcinogenesis.

Abstract: A method of analyzing breast cancer susceptibility or resistance, comprising the steps of obtaining a DNA sample from a patient, genotyping the sample for the presence of the minor allele of single nucleotide polymorphisms rs6476643 or rs2182317, and correlating the identity of the allele with risk assessment data is disclosed.

Abstract: A method of sensitizing tumor cells to radiation thereapy, chemotherapy and immunomodulatory thereapy, comprising the step of exposing the tumor cell to an effective amount of at least one monoterpene or sesquiterpene and treating the tumor cell is disclosed.

Abstract: A method for generating knock-out rodents including rats and mice is disclosed. The method involves mutagenizing a rodent with a mutagen, obtaining progeny of the mutagenized rodent, and identifying, among the progeny, one progeny that carries a loss-of-function modification of a target gene. The preferred mutagen for generating knock-out mice and rats is N-ethyl-N-nitrosourea (ENU). The preferred screening assays for identifying a progeny of a mutagenized animal that carries a loss-of-function modification are yeast truncation assays and yeast functional assays. Knock-out rodents generated by the method of the present invention are also within the scope of the invention.

Abstract: A method of sensitizing tumor cells to radiation thereapy, chemotherapy and immunomodulatory thereapy, comprising the step of exposing the tumor cell to an effective amount of at least one monoterpene or sesquiterpene and treating the tumor cell is disclosed.

Abstract: A method of sensitizing tumor cells to radiation, comprising the step of exposing the tumor cell to an effective amount of at least one monoterpene or sesquiterpene and irradiating the tumor cell, is disclosed.

Abstract: A method of determining the proliferative status of a carcinoma is disclosed. One obtains a patient sample and then quantitatively analyzes the sample for NGAL gene expression product. The amount of NGAL expression product is compared with a standard curve to determine the S-phase value. The sample can be breast tissue or breast fluid aspirate. Alternatively, blood can by analyzed for this marker to diagnose metastasis.

Abstract: An isolated DNA fragment comprising a mammary gland-specific promoter is disclosed. Preferably, this promoter promotes gene expression throughout the estrous cycle in a constant manner. In one embodiment, the promoter comprises nucleotides 1154 through 2967 of SEQ ID NO:1 or 1102 through 2910 of SEQ ID NO:2.

Abstract: Methods are disclosed to identify differentially expressed genes. In one aspect, one uses subtractive hybridization to enrich for candidate genes, followed by a PCR amplified radiolabeled display of cDNA products of the hybridization. Specially modified primer binding regions are used that can be achieved either through use of trimming plasmids or non-symmetric display plasmids.

Abstract: A method of determining the proliferative status of a carcinoma is disclosed. One obtains a patient sample and then quantitatively analyzes the sample for NGAL gene expression product. The amount of NGAL expression product is compared with a standard curve to determine the S-phase value. The sample can be breast tissue or breast fluid aspirate. Alternatively, blood can by analyzed for this marker to diagnose metastasis.

Abstract: A method for causing regression of a leukemia cell tumor is disclosed. This method comprises the step of administering perillyl alcohol to a tumor-containing mammal.

Abstract: A method of causing carcinoma regression is disclosed. One administers an effective amount of perillic acid methyl ester. The use of perillic acid methyl ester is disclosed. A pharmaceutical composition involving perillic acid methyl ester is disclosed.

Abstract: A method for causing regression of a carcinoma is disclosed. This method comprising the step of administering to a carcinoma-containing mammal an effective amount of a compound of the formula: ##STR1## This formula represents perillyl alcohol.

Abstract: A method for producing a recombinant mammal in vivo is disclosed. The mammal has a mammary gland, with mammary epithelial cells lining a duct in that gland One increases the rate of mitosis of the mammary epithelial cells (e.g. by using perphenazine or a mitogen), and one then exposes the mammary epithelial cells in vivo in the gland to a recombinant vector (e.g. a retrovirus vector). The mammary epithelial cells can be pretreated (or simultaneously treated) with polybrene to facilitate infection by virus vectors, and the vector can have a signal sequence which causes foreign proteinaceous material to be secreted into the milk produced by the mammary gland. Also disclosed are recombinant non-human mammals produced by such methods and novel milk products that they produce.