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Effect of Hydroxyurea and Related Compounds on HMC Mammary Tumor Growth and Nucleic Acids in Fischer Rats¹

Squibb Institute for Medical Research, New Brunswick, New Jersey

Hydroxyurea is an effective compound in inhibiting the growth of a transplantable mammary tumor (HMC) in the Fischer rat, the inhibition being dose related and independent of the duration of treatment. Several compounds related to hydroxyurea were tested and compared to the parent compound. 1-Ethyl-1-hydroxyurea and 1-methyl-1-hydroxyurea are more effective than hydroxyurea in causing inhibition of neoplastic growth. The response of the HMC tumor to several other known anticancer agents was also investigated to help characterize this mammary carcinoma.

The effect of hydroxyurea and related compounds upon HMC tumor nucleic acid concentration was studied. The inhibition of neoplastic growth induced by these compounds resulted in an increase in the RNA/mg tumor and also a consistent increase in the RNA/DNA ratio. Nucleic acid analyses were also performed on HMC carcinoma from animals treated with other known antitumor agents. The data are discussed in reference to the proposed mechanism of action of hydroxyurea.

¹ Work supported by Contract No. SA-43-ph-2395 from the Cancer Chemotherapy National Service Center, National Cancer Institute, NIH, Bethesda, Md.

Received 11/15/65. Accepted 5/24/66.